Skip to main content
Top
Published in: BMC Gastroenterology 1/2023

Open Access 01-12-2023 | Colorectal Cancer | Research

Postoperative serum interleukin-6 levels correlate with survival in stage I-III colorectal cancer

Authors: Shouhan Feng, Zeshi Li, Mei Liu, Qianwen Ye, Tianhui Xue, Bing Yan

Published in: BMC Gastroenterology | Issue 1/2023

Login to get access

Abstract

Aims

The preoperative serum levels of inflammatory mediators, including C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), have been demonstrated to be correlated with patient outcomes in colorectal cancer (CRC); however, the prognostic role of these levels has been less well-studied in postoperative settings.

Materials and methods

A total of 122 stage I-III CRC patients were retrospectively enrolled. Serum levels of CRP, PCT and IL-6 were measured after surgery, and their prognostic value was evaluated. Kaplan-Meier analysis was used to determine the differences in disease-free survival (DFS) and overall survival (OS) between patients with different levels of these mediators, and the Cox proportional hazards model was used to estimate the risk factors.

Results

In contrast to CRP and PCT, only the level of IL-6 was significant in predicting DFS (P = 0.01) but not OS (P = 0.07). A total of 66.39% (81/122) of patients were assigned to the low IL-6 group and no significant differences were found in the collected clinicopathological parameters among the low or high IL-6 subgroups. The level of IL-6 was negatively correlated with postoperative (1 w) (R=-0.24, P = 0.02) absolute lymphocyte counts. Patients with low levels of IL-6 had better DFS (log rank = 6.10, P = 0.01) but not OS (log rank = 2.28, P = 0.13). Finally, the level of IL-6 was an independent risk factor for DFS (HR: 1.81, 95% CI: 1.03–3.15, P = 0.04).

Conclusions

Compared to CRP and PCT, the level of IL-6 was observed to be the only significant factor in predicting the prognosis of stage I-III CRC patients after surgery, and a low level of IL-6 was associated with good DFS.
Literature
2.
go back to reference Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.PubMedCrossRef Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.PubMedCrossRef
3.
go back to reference Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64.PubMedCrossRef Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64.PubMedCrossRef
4.
go back to reference Fuglestad AJ, Meltzer S, Ree AH, McMillan DC, Park JH, Kersten C. The clinical value of C-reactive protein and its association with tumour location in patients undergoing curative surgery for colorectal cancer-a ScotScan collaborative study. Acta Oncol. 2022;61(10):1248–55.PubMedCrossRef Fuglestad AJ, Meltzer S, Ree AH, McMillan DC, Park JH, Kersten C. The clinical value of C-reactive protein and its association with tumour location in patients undergoing curative surgery for colorectal cancer-a ScotScan collaborative study. Acta Oncol. 2022;61(10):1248–55.PubMedCrossRef
5.
go back to reference Miyake T, Iida H, Shimizu T, Ueki T, Kojima M, Ohta H, et al. The elevation in preoperative procalcitonin is associated with a poor prognosis for patients undergoing resection for colorectal cancer. Dig Surg. 2021;38(1):80–6.PubMedCrossRef Miyake T, Iida H, Shimizu T, Ueki T, Kojima M, Ohta H, et al. The elevation in preoperative procalcitonin is associated with a poor prognosis for patients undergoing resection for colorectal cancer. Dig Surg. 2021;38(1):80–6.PubMedCrossRef
6.
go back to reference Groblewska M, Mroczko B, Wereszczyńska-Siemiatkowska U, Kedra B, Lukaszewicz M, Baniukiewicz A, et al. Serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels in colorectal adenoma and cancer patients. Clin Chem Lab Med. 2008;46(10):1423–8.PubMedCrossRef Groblewska M, Mroczko B, Wereszczyńska-Siemiatkowska U, Kedra B, Lukaszewicz M, Baniukiewicz A, et al. Serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels in colorectal adenoma and cancer patients. Clin Chem Lab Med. 2008;46(10):1423–8.PubMedCrossRef
7.
go back to reference Lee WS, Baek JH, You DH, Nam MJ. Prognostic value of circulating cytokines for stage III colon cancer. J Surg Res. 2013;182(1):49–54.PubMedCrossRef Lee WS, Baek JH, You DH, Nam MJ. Prognostic value of circulating cytokines for stage III colon cancer. J Surg Res. 2013;182(1):49–54.PubMedCrossRef
8.
go back to reference Kwon KA, Kim SH, Oh SY, Lee S, Han JY, Kim KH, et al. Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer. BMC Cancer. 2010;10:203.PubMedPubMedCentralCrossRef Kwon KA, Kim SH, Oh SY, Lee S, Han JY, Kim KH, et al. Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer. BMC Cancer. 2010;10:203.PubMedPubMedCentralCrossRef
9.
go back to reference Yasui K, Shida D, Nakamura Y, Ahiko Y, Tsukamoto S, Kanemitsu Y. Postoperative, but not preoperative, inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients. Br J Cancer. 2021;124(5):933–41.PubMedCrossRef Yasui K, Shida D, Nakamura Y, Ahiko Y, Tsukamoto S, Kanemitsu Y. Postoperative, but not preoperative, inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients. Br J Cancer. 2021;124(5):933–41.PubMedCrossRef
10.
go back to reference Hayama T, Hashiguchi Y, Okada Y, Ono K, Nemoto K, Shimada R, et al. Significance of the 7th postoperative day neutrophil-to-lymphocyte ratio in colorectal cancer. Int J Colorectal Dis. 2020;35(1):119–24.PubMedCrossRef Hayama T, Hashiguchi Y, Okada Y, Ono K, Nemoto K, Shimada R, et al. Significance of the 7th postoperative day neutrophil-to-lymphocyte ratio in colorectal cancer. Int J Colorectal Dis. 2020;35(1):119–24.PubMedCrossRef
11.
go back to reference Takakura Y, Hinoi T, Egi H, Shimomura M, Adachi T, Saito Y, et al. Procalcitonin as a predictive marker for surgical site infection in elective colorectal cancer surgery. Langenbecks Arch Surg. 2013;398(6):833–9.PubMedCrossRef Takakura Y, Hinoi T, Egi H, Shimomura M, Adachi T, Saito Y, et al. Procalcitonin as a predictive marker for surgical site infection in elective colorectal cancer surgery. Langenbecks Arch Surg. 2013;398(6):833–9.PubMedCrossRef
12.
go back to reference Domínguez-Comesaña E, Estevez-Fernández SM, López-Gómez V, Ballinas-Miranda J, Domínguez-Fernández R. Procalcitonin and C-reactive protein as early markers of postoperative intra-abdominal infection in patients operated on colorectal cancer. Int J Colorectal Dis. 2017;32(12):1771–4.PubMedCrossRef Domínguez-Comesaña E, Estevez-Fernández SM, López-Gómez V, Ballinas-Miranda J, Domínguez-Fernández R. Procalcitonin and C-reactive protein as early markers of postoperative intra-abdominal infection in patients operated on colorectal cancer. Int J Colorectal Dis. 2017;32(12):1771–4.PubMedCrossRef
13.
go back to reference Galizia G, Orditura M, Romano C, Lieto E, Castellano P, Pelosio L, et al. Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin Immunol. 2002;102(2):169–78.PubMedCrossRef Galizia G, Orditura M, Romano C, Lieto E, Castellano P, Pelosio L, et al. Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin Immunol. 2002;102(2):169–78.PubMedCrossRef
14.
go back to reference Ding S, Ma H, Wang G, Yu Z, Li K, Huang A. Effect of remifentanil combined anesthesia on cytokines and oxidative stress in patients undergoing laparoscopic surgery for colon cancer. J Coll Physicians Surg Pak. 2019;29(1):8–11.PubMedCrossRef Ding S, Ma H, Wang G, Yu Z, Li K, Huang A. Effect of remifentanil combined anesthesia on cytokines and oxidative stress in patients undergoing laparoscopic surgery for colon cancer. J Coll Physicians Surg Pak. 2019;29(1):8–11.PubMedCrossRef
15.
go back to reference Margarit SC, Vasian HN, Balla E, Vesa S, Ionescu DC. The influence of total intravenous anaesthesia and isoflurane anaesthesia on plasma interleukin-6 and interleukin-10 concentrations after colorectal surgery for cancer: a randomised controlled trial. Eur J Anaesthesiol. 2014;31(12):678–84.PubMedCrossRef Margarit SC, Vasian HN, Balla E, Vesa S, Ionescu DC. The influence of total intravenous anaesthesia and isoflurane anaesthesia on plasma interleukin-6 and interleukin-10 concentrations after colorectal surgery for cancer: a randomised controlled trial. Eur J Anaesthesiol. 2014;31(12):678–84.PubMedCrossRef
16.
go back to reference Hermunen K, Soveri LM, Boisen MK, Mustonen HK, Dehlendorff C, Haglund CH, et al. Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer. Acta Oncol. 2020;59(12):1416–23.PubMedCrossRef Hermunen K, Soveri LM, Boisen MK, Mustonen HK, Dehlendorff C, Haglund CH, et al. Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer. Acta Oncol. 2020;59(12):1416–23.PubMedCrossRef
17.
go back to reference Hua X, Kratz M, Malen RC, Dai JY, Lindström S, Zheng Y, et al. Association between post-treatment circulating biomarkers of inflammation and survival among stage II-III colorectal cancer patients. Br J Cancer. 2021;125(6):806–15.PubMedPubMedCentralCrossRef Hua X, Kratz M, Malen RC, Dai JY, Lindström S, Zheng Y, et al. Association between post-treatment circulating biomarkers of inflammation and survival among stage II-III colorectal cancer patients. Br J Cancer. 2021;125(6):806–15.PubMedPubMedCentralCrossRef
18.
go back to reference Xu R, You JH, Li F, Yan B. Postoperative fasting blood glucose predicts prognosis in stage I-III colorectal cancer patients undergoing resection. Gastroenterol Res Pract. 2020;2020:2482409.PubMedPubMedCentralCrossRef Xu R, You JH, Li F, Yan B. Postoperative fasting blood glucose predicts prognosis in stage I-III colorectal cancer patients undergoing resection. Gastroenterol Res Pract. 2020;2020:2482409.PubMedPubMedCentralCrossRef
19.
go back to reference Zhang Y, Liu Y, Qiu X, Yan B. Concurrent comparison of the prognostic values of tumor budding, tumor stroma ratio, tumor infiltrating pattern and lymphocyte-to-monocyte ratio in colorectal cancer patients. Technol Cancer Res Treat. 2021;20:15330338211045826.PubMedPubMedCentralCrossRef Zhang Y, Liu Y, Qiu X, Yan B. Concurrent comparison of the prognostic values of tumor budding, tumor stroma ratio, tumor infiltrating pattern and lymphocyte-to-monocyte ratio in colorectal cancer patients. Technol Cancer Res Treat. 2021;20:15330338211045826.PubMedPubMedCentralCrossRef
20.
go back to reference Huang X, Huan Y, Liu L, Ye Q, Guo J, Yan B. Preoperative low absolute lymphocyte count to fibrinogen ratio correlated with poor survival in nonmetastatic colorectal cancer. World J Surg Oncol. 2022;20(1):309.PubMedPubMedCentralCrossRef Huang X, Huan Y, Liu L, Ye Q, Guo J, Yan B. Preoperative low absolute lymphocyte count to fibrinogen ratio correlated with poor survival in nonmetastatic colorectal cancer. World J Surg Oncol. 2022;20(1):309.PubMedPubMedCentralCrossRef
21.
go back to reference Hailun Xie, Huang S, Yuan G, Tang S, Gan J. Prognostic significance of preoperative fibrinogen-to-prealbumin ratio in patients with stage I-III colorectal cancer undergoing surgical resection: a retrospective cohort study. Biomed Res Int. 2021;2021:3905353. Hailun Xie, Huang S, Yuan G, Tang S, Gan J. Prognostic significance of preoperative fibrinogen-to-prealbumin ratio in patients with stage I-III colorectal cancer undergoing surgical resection: a retrospective cohort study. Biomed Res Int. 2021;2021:3905353.
22.
go back to reference McSorley ST, Watt DG, Horgan PG, McMillan DC. Postoperative systemic inflammatory response, complication severity, and survival following surgery for colorectal cancer. Ann Surg Oncol. 2016;23(9):2832–40.PubMedPubMedCentralCrossRef McSorley ST, Watt DG, Horgan PG, McMillan DC. Postoperative systemic inflammatory response, complication severity, and survival following surgery for colorectal cancer. Ann Surg Oncol. 2016;23(9):2832–40.PubMedPubMedCentralCrossRef
23.
go back to reference Yamamoto M, Saito H, Uejima C, Tanio A, Takaya S, Sakamoto T, et al. Prognostic value of the combination of pre- and postoperative C-reactive protein in colorectal cancer patients. Surg Today. 2018;48(11):986–93.PubMedCrossRef Yamamoto M, Saito H, Uejima C, Tanio A, Takaya S, Sakamoto T, et al. Prognostic value of the combination of pre- and postoperative C-reactive protein in colorectal cancer patients. Surg Today. 2018;48(11):986–93.PubMedCrossRef
24.
go back to reference Matsubara D, Arita T, Nakanishi M, Kuriu Y, Murayama Y, Kudou M, et al. The impact of postoperative inflammation on recurrence in patients with colorectal cancer. Int J Clin Oncol. 2020;25(4):602–13.PubMedCrossRef Matsubara D, Arita T, Nakanishi M, Kuriu Y, Murayama Y, Kudou M, et al. The impact of postoperative inflammation on recurrence in patients with colorectal cancer. Int J Clin Oncol. 2020;25(4):602–13.PubMedCrossRef
25.
go back to reference Nakamura Y, Yamaura T, Kinjo Y, Kawase M, Kanto S, Kuroda N. Impact of severe postoperative inflammatory response on recurrence after curative resection of colorectal cancer. Int J Colorectal Dis. 2022;37(11):2375–86.PubMedCrossRef Nakamura Y, Yamaura T, Kinjo Y, Kawase M, Kanto S, Kuroda N. Impact of severe postoperative inflammatory response on recurrence after curative resection of colorectal cancer. Int J Colorectal Dis. 2022;37(11):2375–86.PubMedCrossRef
26.
go back to reference Aoki S, Migita K, Ueno M, Yasuda S, Fujimoto K, Doi S, et al. Postoperative serum C-reactive protein level predicts long-term outcomes in colorectal cancer patients. Gan To Kagaku Ryoho. 2020;47(13):2113–6.PubMed Aoki S, Migita K, Ueno M, Yasuda S, Fujimoto K, Doi S, et al. Postoperative serum C-reactive protein level predicts long-term outcomes in colorectal cancer patients. Gan To Kagaku Ryoho. 2020;47(13):2113–6.PubMed
27.
go back to reference Bae JH, Lee CS, Han SR, Park SM, Lee YS, Lee IK. Differences in the prognostic impact of post-operative systemic inflammation and infection in colorectal cancer patients: using white blood cell counts and procalcitonin levels. Surg Oncol. 2020;35:374–81.PubMedCrossRef Bae JH, Lee CS, Han SR, Park SM, Lee YS, Lee IK. Differences in the prognostic impact of post-operative systemic inflammation and infection in colorectal cancer patients: using white blood cell counts and procalcitonin levels. Surg Oncol. 2020;35:374–81.PubMedCrossRef
28.
go back to reference Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352(5):476–87.PubMedCrossRef Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352(5):476–87.PubMedCrossRef
29.
go back to reference Li C, Xu Q, Chen L, Luo C, Ying J, Liu J. C-reactive protein (CRP) as a prognostic factor for colorectal cancer after surgical resection of pulmonary metastases. Bull Cancer. 2017;104(3):232–6.PubMedCrossRef Li C, Xu Q, Chen L, Luo C, Ying J, Liu J. C-reactive protein (CRP) as a prognostic factor for colorectal cancer after surgical resection of pulmonary metastases. Bull Cancer. 2017;104(3):232–6.PubMedCrossRef
30.
go back to reference Woo HD, Kim K, Kim J. Association between preoperative C-reactive protein level and colorectal cancer survival: a meta-analysis. Cancer Causes Control. 2015;26(11):1661–70.PubMedCrossRef Woo HD, Kim K, Kim J. Association between preoperative C-reactive protein level and colorectal cancer survival: a meta-analysis. Cancer Causes Control. 2015;26(11):1661–70.PubMedCrossRef
31.
go back to reference Shibutani M, Maeda K, Nagahara H, Ohtani H, Sugano K, Ikeya T, et al. Elevated preoperative serum C-reactive protein levels are associated with poor survival in patients with colorectal cancer. Hepatogastroenterology. 2014;61(136):2236–40.PubMed Shibutani M, Maeda K, Nagahara H, Ohtani H, Sugano K, Ikeya T, et al. Elevated preoperative serum C-reactive protein levels are associated with poor survival in patients with colorectal cancer. Hepatogastroenterology. 2014;61(136):2236–40.PubMed
32.
go back to reference Platt JJ, Ramanathan ML, Crosbie RA, Anderson JH, McKee RF, Horgan PG, et al. C-reactive protein as a predictor of postoperative infective complications after curative resection in patients with colorectal cancer. Ann Surg Oncol. 2012;19(13):4168–77.PubMedCrossRef Platt JJ, Ramanathan ML, Crosbie RA, Anderson JH, McKee RF, Horgan PG, et al. C-reactive protein as a predictor of postoperative infective complications after curative resection in patients with colorectal cancer. Ann Surg Oncol. 2012;19(13):4168–77.PubMedCrossRef
33.
go back to reference Park BS, Cho SH, Lee SH, Son GM, Kim HS. Role of C-reactive protein, white blood cell counts, and serum glucose levels as early predictors of infectious complications after laparoscopic colorectal surgery for colorectal cancer. Am Surg. 2022:31348221135786. Park BS, Cho SH, Lee SH, Son GM, Kim HS. Role of C-reactive protein, white blood cell counts, and serum glucose levels as early predictors of infectious complications after laparoscopic colorectal surgery for colorectal cancer. Am Surg. 2022:31348221135786.
34.
go back to reference Keramidaris D, Koronakis N, Lagoudianakis EE, Pappas A, Koukoutsis I, Chrysikos I, et al. Procalcitonin in patients with colorectal cancer. J BUON. 2013;18(3):623–8.PubMed Keramidaris D, Koronakis N, Lagoudianakis EE, Pappas A, Koukoutsis I, Chrysikos I, et al. Procalcitonin in patients with colorectal cancer. J BUON. 2013;18(3):623–8.PubMed
35.
go back to reference Fujii T, Yajima R, Tabe Y, Yamaguchi S, Tsutsumi S, Asao T, et al. Elevated C-reactive protein is associated with the tumor depth of invasion but not with disease recurrence in stage II and III colorectal cancer. Hepatogastroenterology. 2013;60(126):1343–7.PubMed Fujii T, Yajima R, Tabe Y, Yamaguchi S, Tsutsumi S, Asao T, et al. Elevated C-reactive protein is associated with the tumor depth of invasion but not with disease recurrence in stage II and III colorectal cancer. Hepatogastroenterology. 2013;60(126):1343–7.PubMed
36.
go back to reference Swede H, Hajduk AM, Sharma J, Rawal S, Rasool H, Vella AT. Baseline serum C-reactive protein and death from colorectal cancer in the NHANES III cohort. Int J Cancer. 2014;134(8):1862–70.PubMedCrossRef Swede H, Hajduk AM, Sharma J, Rawal S, Rasool H, Vella AT. Baseline serum C-reactive protein and death from colorectal cancer in the NHANES III cohort. Int J Cancer. 2014;134(8):1862–70.PubMedCrossRef
37.
go back to reference Hua X, Dai JY, Lindström S, Harrison TA, Lin Y, Alberts SR, et al. Genetically predicted circulating c-reactive protein concentration and colorectal cancer survival: a mendelian randomization consortium study. Cancer Epidemiol Biomarkers Prev. 2021;30(7):1349–58.PubMedPubMedCentralCrossRef Hua X, Dai JY, Lindström S, Harrison TA, Lin Y, Alberts SR, et al. Genetically predicted circulating c-reactive protein concentration and colorectal cancer survival: a mendelian randomization consortium study. Cancer Epidemiol Biomarkers Prev. 2021;30(7):1349–58.PubMedPubMedCentralCrossRef
38.
go back to reference Mehigan BJ, Hartley JE, Drew PJ, Saleh A, Dore PC, Lee PW, et al. Changes in T cell subsets, interleukin-6 and C-reactive protein after laparoscopic and open colorectal resection for malignancy. Surg Endosc. 2001;15(11):1289–93.PubMedCrossRef Mehigan BJ, Hartley JE, Drew PJ, Saleh A, Dore PC, Lee PW, et al. Changes in T cell subsets, interleukin-6 and C-reactive protein after laparoscopic and open colorectal resection for malignancy. Surg Endosc. 2001;15(11):1289–93.PubMedCrossRef
39.
go back to reference Kamińska J, Kowalska MM, Nowacki MP, Chwaliński MG, Rysińska A, Fuksiewicz M. CRP, TNF-alpha, IL-1ra, IL-6, IL-8 and IL-10 in blood serum of colorectal cancer patients. Pathol Oncol Res. 2000;6(1):38–41.PubMedCrossRef Kamińska J, Kowalska MM, Nowacki MP, Chwaliński MG, Rysińska A, Fuksiewicz M. CRP, TNF-alpha, IL-1ra, IL-6, IL-8 and IL-10 in blood serum of colorectal cancer patients. Pathol Oncol Res. 2000;6(1):38–41.PubMedCrossRef
40.
go back to reference Guthrie GJ, Roxburgh CS, Richards CH, Horgan PG, McMillan DC. Circulating IL-6 concentrations link tumour necrosis and systemic and local inflammatory responses in patients undergoing resection for colorectal cancer. Br J Cancer. 2013;109(1):131–7.PubMedPubMedCentralCrossRef Guthrie GJ, Roxburgh CS, Richards CH, Horgan PG, McMillan DC. Circulating IL-6 concentrations link tumour necrosis and systemic and local inflammatory responses in patients undergoing resection for colorectal cancer. Br J Cancer. 2013;109(1):131–7.PubMedPubMedCentralCrossRef
41.
go back to reference Becker C, Fantini MC, Wirtz S, Nikolaev A, Lehr HA, Galle PR, et al. IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle. 2005;4(2):217–20.PubMedCrossRef Becker C, Fantini MC, Wirtz S, Nikolaev A, Lehr HA, Galle PR, et al. IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle. 2005;4(2):217–20.PubMedCrossRef
42.
go back to reference Ashizawa T, Okada R, Suzuki Y, Takagi M, Yamazaki T, Sumi T, et al. Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6. Acta Med Okayama. 2006;60(6):325–30.PubMed Ashizawa T, Okada R, Suzuki Y, Takagi M, Yamazaki T, Sumi T, et al. Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6. Acta Med Okayama. 2006;60(6):325–30.PubMed
43.
go back to reference Nagasaki T, Hara M, Nakanishi H, Takahashi H, Sato M, Takeyama H. Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction. Br J Cancer. 2014;110(2):469–78.PubMedCrossRef Nagasaki T, Hara M, Nakanishi H, Takahashi H, Sato M, Takeyama H. Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction. Br J Cancer. 2014;110(2):469–78.PubMedCrossRef
44.
go back to reference Hara M, Nagasaki T, Shiga K, Takahashi H, Takeyama H. High serum levels of interleukin-6 in patients with advanced or metastatic colorectal cancer: the effect on the outcome and the response to chemotherapy plus bevacizumab. Surg Today. 2017;47(4):483–9.PubMedCrossRef Hara M, Nagasaki T, Shiga K, Takahashi H, Takeyama H. High serum levels of interleukin-6 in patients with advanced or metastatic colorectal cancer: the effect on the outcome and the response to chemotherapy plus bevacizumab. Surg Today. 2017;47(4):483–9.PubMedCrossRef
45.
go back to reference Li S, Tian J, Zhang H, Zhou S, Wang X, Zhang L, et al. Down-regulating IL-6/GP130 targets improved the anti-tumor effects of 5-fluorouracil in colon cancer. Apoptosis. 2018;23(5–6):356–74.PubMedCrossRef Li S, Tian J, Zhang H, Zhou S, Wang X, Zhang L, et al. Down-regulating IL-6/GP130 targets improved the anti-tumor effects of 5-fluorouracil in colon cancer. Apoptosis. 2018;23(5–6):356–74.PubMedCrossRef
46.
go back to reference Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Scott Shaffer J, et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019;51(7):1113–22.PubMedPubMedCentralCrossRef Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Scott Shaffer J, et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019;51(7):1113–22.PubMedPubMedCentralCrossRef
47.
go back to reference Peach G, Kim C, Zacharakis E, Purkayastha S, Ziprin P. Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. Br J Cancer. 2010;102(9):1327–34.PubMedPubMedCentralCrossRef Peach G, Kim C, Zacharakis E, Purkayastha S, Ziprin P. Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. Br J Cancer. 2010;102(9):1327–34.PubMedPubMedCentralCrossRef
48.
go back to reference Abdalla TSA, Meiners J, Riethdorf S, König A, Melling N, Gorges T, et al. Prognostic value of preoperative circulating tumor cells counts in patients with UICC stage I-IV colorectal cancer. PLoS ONE. 2021;16(6):e0252897.PubMedPubMedCentralCrossRef Abdalla TSA, Meiners J, Riethdorf S, König A, Melling N, Gorges T, et al. Prognostic value of preoperative circulating tumor cells counts in patients with UICC stage I-IV colorectal cancer. PLoS ONE. 2021;16(6):e0252897.PubMedPubMedCentralCrossRef
49.
go back to reference Li YC, Zou JM, Luo C, Shu Y, Luo J, Qin J, et al. Circulating tumor cells promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation. Oncotarget. 2017;8(17):28418–30.PubMedPubMedCentralCrossRef Li YC, Zou JM, Luo C, Shu Y, Luo J, Qin J, et al. Circulating tumor cells promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation. Oncotarget. 2017;8(17):28418–30.PubMedPubMedCentralCrossRef
50.
go back to reference Koren E, Fuchs Y. The bad seed: Cancer stem cells in tumor development and resistance. Drug Resist Updat. 2016;28:1–12.PubMedCrossRef Koren E, Fuchs Y. The bad seed: Cancer stem cells in tumor development and resistance. Drug Resist Updat. 2016;28:1–12.PubMedCrossRef
51.
go back to reference Du L, Cheng Q, Zheng H, Liu J, Liu L, Chen Q. Targeting stemness of cancer stem cells to fight colorectal cancers. Semin Cancer Biol. 2022;82:150–61.PubMedCrossRef Du L, Cheng Q, Zheng H, Liu J, Liu L, Chen Q. Targeting stemness of cancer stem cells to fight colorectal cancers. Semin Cancer Biol. 2022;82:150–61.PubMedCrossRef
52.
go back to reference Grillet F, Bayet E, Villeronce O, Zappia L, Lagerqvist EL, Lunke S, et al. Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Gut. 2017;66(10):1802–10.PubMedCrossRef Grillet F, Bayet E, Villeronce O, Zappia L, Lagerqvist EL, Lunke S, et al. Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Gut. 2017;66(10):1802–10.PubMedCrossRef
53.
go back to reference Ning Y, Zhang W, Hanna DL, Yang D, Okazaki S, Berger MD, et al. Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients. Pharmacogenomics J. 2018;18(1):29–34.PubMedCrossRef Ning Y, Zhang W, Hanna DL, Yang D, Okazaki S, Berger MD, et al. Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients. Pharmacogenomics J. 2018;18(1):29–34.PubMedCrossRef
54.
go back to reference Kim B, Seo Y, Kwon JH, Shin Y, Kim S, Park SJ, et al. IL-6 and IL-8, secreted by myofibroblasts in the tumor microenvironment, activate HES1 to expand the cancer stem cell population in early colorectal tumor. Mol Carcinog. 2021;60(3):188–200.PubMedCrossRef Kim B, Seo Y, Kwon JH, Shin Y, Kim S, Park SJ, et al. IL-6 and IL-8, secreted by myofibroblasts in the tumor microenvironment, activate HES1 to expand the cancer stem cell population in early colorectal tumor. Mol Carcinog. 2021;60(3):188–200.PubMedCrossRef
55.
go back to reference Di Franco S, Bianca P, Sardina DS, Turdo A, Gaggianesi M, Veschi V, et al. Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery. Nat Commun. 2021;12(1):5006.PubMedPubMedCentralCrossRef Di Franco S, Bianca P, Sardina DS, Turdo A, Gaggianesi M, Veschi V, et al. Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery. Nat Commun. 2021;12(1):5006.PubMedPubMedCentralCrossRef
56.
go back to reference Wang T, Song P, Zhong T, Wang X, Xiang X, Liu Q, et al. The inflammatory cytokine IL-6 induces FRA1 deacetylation promoting colorectal cancer stem-like properties. Oncogene. 2019;38(25):4932–47.PubMedPubMedCentralCrossRef Wang T, Song P, Zhong T, Wang X, Xiang X, Liu Q, et al. The inflammatory cytokine IL-6 induces FRA1 deacetylation promoting colorectal cancer stem-like properties. Oncogene. 2019;38(25):4932–47.PubMedPubMedCentralCrossRef
57.
go back to reference Huynh PT, Beswick EJ, Coronado YA, Johnson P, O’Connell MR, Watts T, et al. CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. Int J Cancer. 2016;138(8):1971–81.PubMedCrossRef Huynh PT, Beswick EJ, Coronado YA, Johnson P, O’Connell MR, Watts T, et al. CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. Int J Cancer. 2016;138(8):1971–81.PubMedCrossRef
58.
go back to reference Inoda S, Hirohashi Y, Torigoe T, Morita R, Takahashi A, Asanuma H, et al. Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells. Am J Pathol. 2011;178(4):1805–13.PubMedPubMedCentralCrossRef Inoda S, Hirohashi Y, Torigoe T, Morita R, Takahashi A, Asanuma H, et al. Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells. Am J Pathol. 2011;178(4):1805–13.PubMedPubMedCentralCrossRef
59.
go back to reference Katayama C, Yokobori T, Ozawa N, Suga K, Shiraishi T, Okada T, et al. Low level of stromal lectin-like oxidized LDL receptor 1 and CD8 + cytotoxic T-lymphocytes indicate poor prognosis of colorectal cancer. Cancer Rep (Hoboken). 2021;4(4):e1364.PubMed Katayama C, Yokobori T, Ozawa N, Suga K, Shiraishi T, Okada T, et al. Low level of stromal lectin-like oxidized LDL receptor 1 and CD8 + cytotoxic T-lymphocytes indicate poor prognosis of colorectal cancer. Cancer Rep (Hoboken). 2021;4(4):e1364.PubMed
60.
go back to reference Jewell AP, Worman CP, Giles FJ, Goldstone AH. Serum levels of TNF, IL-6 and sCD23 correlate with changes in lymphocyte count in patients with B-cell chronic lymphocytic leukaemia receiving interferon-alpha therapy. Leuk Lymphoma. 1997;24(3–4):327–33.PubMedCrossRef Jewell AP, Worman CP, Giles FJ, Goldstone AH. Serum levels of TNF, IL-6 and sCD23 correlate with changes in lymphocyte count in patients with B-cell chronic lymphocytic leukaemia receiving interferon-alpha therapy. Leuk Lymphoma. 1997;24(3–4):327–33.PubMedCrossRef
61.
go back to reference Yu Y, Wang S, Su N, Pan S, Tu B, Zhao J, et al. Increased circulating levels of CRP and IL-6 and decreased frequencies of T and B lymphocyte subsets are associated with immune-related adverse events during combination therapy with PD-1 inhibitors for liver cancer. Front Oncol. 2022;12:906824.PubMedPubMedCentralCrossRef Yu Y, Wang S, Su N, Pan S, Tu B, Zhao J, et al. Increased circulating levels of CRP and IL-6 and decreased frequencies of T and B lymphocyte subsets are associated with immune-related adverse events during combination therapy with PD-1 inhibitors for liver cancer. Front Oncol. 2022;12:906824.PubMedPubMedCentralCrossRef
62.
go back to reference Bent EH, Millán-Barea LR, Zhuang I, Goulet DR, Fröse J, Hemann MT. Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy. Nat Commun. 2021;12(1):6218.PubMedPubMedCentralCrossRef Bent EH, Millán-Barea LR, Zhuang I, Goulet DR, Fröse J, Hemann MT. Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy. Nat Commun. 2021;12(1):6218.PubMedPubMedCentralCrossRef
63.
go back to reference Naszai M, Kurjan A, Maughan TS. The prognostic utility of pre-treatment neutrophil-to-lymphocyte-ratio (NLR) in colorectal cancer: a systematic review and meta-analysis. Cancer Med. 2021;10(17):5983–97.PubMedPubMedCentralCrossRef Naszai M, Kurjan A, Maughan TS. The prognostic utility of pre-treatment neutrophil-to-lymphocyte-ratio (NLR) in colorectal cancer: a systematic review and meta-analysis. Cancer Med. 2021;10(17):5983–97.PubMedPubMedCentralCrossRef
64.
go back to reference Gülben K, Berberoğlu U, Öndeş B, Uyar O, Güler OC, Turanlı S. Preoperative neutrophil-to-lymphocyte ratio as a predictive factor for survival in nonmetastatic colorectal cancer. J Cancer Res Ther. 2020;16(Supplement):189–S193.CrossRef Gülben K, Berberoğlu U, Öndeş B, Uyar O, Güler OC, Turanlı S. Preoperative neutrophil-to-lymphocyte ratio as a predictive factor for survival in nonmetastatic colorectal cancer. J Cancer Res Ther. 2020;16(Supplement):189–S193.CrossRef
65.
go back to reference Wu Q, Hu T, Zheng E, Deng X, Wang Z. Prognostic role of the lymphocyte-to-monocyte ratio in colorectal cancer: an up-to-date meta-analysis. Med (Baltim). 2017;96(22):e7051.CrossRef Wu Q, Hu T, Zheng E, Deng X, Wang Z. Prognostic role of the lymphocyte-to-monocyte ratio in colorectal cancer: an up-to-date meta-analysis. Med (Baltim). 2017;96(22):e7051.CrossRef
66.
go back to reference Song W, Wang K, Zhang RJ, Zou SB. Prognostic value of the lymphocyte monocyte ratio in patients with colorectal cancer: a meta-analysis. Med (Baltim). 2016;95(49):e5540.CrossRef Song W, Wang K, Zhang RJ, Zou SB. Prognostic value of the lymphocyte monocyte ratio in patients with colorectal cancer: a meta-analysis. Med (Baltim). 2016;95(49):e5540.CrossRef
67.
go back to reference Shinji S, Ueda Y, Yamada T, Koizumi M, Yokoyama Y, Takahashi G, Hotta M, Iwai T, Hara K, Takeda K, Okusa M, Kan H, Uchida E. Combined use of preoperative lymphocyte counts and the post/preoperative lymphocyte count ratio as a prognostic marker of recurrence after curative resection of stage II colon cancer. Oncotarget. 2017;9(2):2553–64.PubMedPubMedCentralCrossRef Shinji S, Ueda Y, Yamada T, Koizumi M, Yokoyama Y, Takahashi G, Hotta M, Iwai T, Hara K, Takeda K, Okusa M, Kan H, Uchida E. Combined use of preoperative lymphocyte counts and the post/preoperative lymphocyte count ratio as a prognostic marker of recurrence after curative resection of stage II colon cancer. Oncotarget. 2017;9(2):2553–64.PubMedPubMedCentralCrossRef
68.
go back to reference Leitch EF, Chakrabarti M, Crozier JE, McKee RF, Anderson JH, Horgan PG, et al. Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer. 2007;97(9):1266–70.PubMedPubMedCentralCrossRef Leitch EF, Chakrabarti M, Crozier JE, McKee RF, Anderson JH, Horgan PG, et al. Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer. 2007;97(9):1266–70.PubMedPubMedCentralCrossRef
69.
go back to reference Cha YJ, Park EJ, Baik SH, Lee KY, Kang J. Clinical significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with stage III colon cancer who underwent surgery followed by FOLFOX chemotherapy. Sci Rep. 2019;9(1):11617.PubMedPubMedCentralCrossRef Cha YJ, Park EJ, Baik SH, Lee KY, Kang J. Clinical significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with stage III colon cancer who underwent surgery followed by FOLFOX chemotherapy. Sci Rep. 2019;9(1):11617.PubMedPubMedCentralCrossRef
70.
go back to reference Syk I, Mangell P, Bjartell A, Jeppsson B. Systemic interleukin-6 response to colorectal surgery originates from the bowel. Dig Surg. 2002;19(3):210–5.PubMedCrossRef Syk I, Mangell P, Bjartell A, Jeppsson B. Systemic interleukin-6 response to colorectal surgery originates from the bowel. Dig Surg. 2002;19(3):210–5.PubMedCrossRef
71.
go back to reference Zhu P, Miao W, Gu F, Xing C. Changes of serum and peritoneal inflammatory mediators in laparoscopic radical resection for right colon carcinoma. J Minim Access Surg. 2018;15(2):115–8. Zhu P, Miao W, Gu F, Xing C. Changes of serum and peritoneal inflammatory mediators in laparoscopic radical resection for right colon carcinoma. J Minim Access Surg. 2018;15(2):115–8.
72.
go back to reference Click B, Pinsky PF, Hickey T, Doroudi M, Schoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319(19):2021–31.PubMedPubMedCentralCrossRef Click B, Pinsky PF, Hickey T, Doroudi M, Schoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319(19):2021–31.PubMedPubMedCentralCrossRef
73.
go back to reference Corley DA, Jensen CD, Marks AR, Zhao WK, Lee JK, Doubeni CA, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370(14):1298–306.PubMedPubMedCentralCrossRef Corley DA, Jensen CD, Marks AR, Zhao WK, Lee JK, Doubeni CA, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370(14):1298–306.PubMedPubMedCentralCrossRef
74.
go back to reference Marques-Antunes J, Libânio D, Gonçalves P, Dinis-Ribeiro M, Pimentel-Nunes P. Incidence and predictors of adenoma after surgery for colorectal cancer. Eur J Gastroenterol Hepatol. 2017;29(8):932–8.PubMedCrossRef Marques-Antunes J, Libânio D, Gonçalves P, Dinis-Ribeiro M, Pimentel-Nunes P. Incidence and predictors of adenoma after surgery for colorectal cancer. Eur J Gastroenterol Hepatol. 2017;29(8):932–8.PubMedCrossRef
75.
go back to reference Facciorusso A, Di Maso M, Serviddio G, Vendemiale G, Spada C, Costamagna G, et al. Factors associated with recurrence of advanced colorectal adenoma after endoscopic resection. Clin Gastroenterol Hepatol. 2016;14(8):1148–1154e4.PubMedCrossRef Facciorusso A, Di Maso M, Serviddio G, Vendemiale G, Spada C, Costamagna G, et al. Factors associated with recurrence of advanced colorectal adenoma after endoscopic resection. Clin Gastroenterol Hepatol. 2016;14(8):1148–1154e4.PubMedCrossRef
76.
go back to reference Groblewska M, Mroczko B, Wereszczyńska-Siemiatkowska U, Kedra B, Lukaszewicz M, Baniukiewicz A, Szmitkowski M. Serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels in colorectal adenoma and cancer patients. Clin Chem Lab Med. 2008;46(10):1423–8.PubMedCrossRef Groblewska M, Mroczko B, Wereszczyńska-Siemiatkowska U, Kedra B, Lukaszewicz M, Baniukiewicz A, Szmitkowski M. Serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels in colorectal adenoma and cancer patients. Clin Chem Lab Med. 2008;46(10):1423–8.PubMedCrossRef
77.
go back to reference Bobe G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, Colburn NH, Cross AJ. Interleukin-6 as a potential indicator for prevention of high-risk adenoma recurrence by dietary flavonols in the polyp prevention trial. Cancer Prev Res (Phila). 2010;3(6):764–75.PubMedCrossRef Bobe G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, Colburn NH, Cross AJ. Interleukin-6 as a potential indicator for prevention of high-risk adenoma recurrence by dietary flavonols in the polyp prevention trial. Cancer Prev Res (Phila). 2010;3(6):764–75.PubMedCrossRef
Metadata
Title
Postoperative serum interleukin-6 levels correlate with survival in stage I-III colorectal cancer
Authors
Shouhan Feng
Zeshi Li
Mei Liu
Qianwen Ye
Tianhui Xue
Bing Yan
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2023
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-023-02800-9

Other articles of this Issue 1/2023

BMC Gastroenterology 1/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.