Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Identification of prognostic inflammatory factors in colorectal liver metastases

Authors: Trevor D Hamilton, Derek Leugner, Karen Kopciuk, Elijah Dixon, Francis R Sutherland, Oliver F Bathe

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

The modified Glasgow Prognostic Score (mGPS) has been reported to be an important prognostic indicator in a number of tumor types, including colorectal cancer (CRC). The features of the inflammatory state thought to accompany elevated C-reactive protein (CRP), a key feature of mGPS, were characterized in patients with colorectal liver metastases. Additional inflammatory mediators that contribute to prognosis were explored.

Methods

In sera from 69 patients with colorectal liver metastases, a panel of 42 inflammatory mediators were quantified as a function of CRP levels, and as a function of disease-free survival. Multivariate statistical methods were used to determine association of each mediator with elevated CRP and truncated disease-free survival.

Results

Elevated CRP was confirmed to be a strong predictor of survival (HR 4.00, p = 0.001) and recurrence (HR 3.30, p = 0.002). The inflammatory state associated with elevated CRP was comprised of raised IL-1β, IL-6, IL-12 and IL-15. In addition, elevated IL-8 and PDGF-AB/BB and decreased eotaxin and IP-10 were associated with worse disease-free and overall survival.

Conclusions

Elevated CRP is associated with a proinflammatory state. The inflammatory state is an important prognostic indicator in CRC liver metastases. The individual contributions of tumor biology and the host to this inflammatory response will require further investigation.
Appendix
Available only for authorised users
Literature
1.
Finlay IG, McArdle CS: Occult hepatic metastases in colorectal carcinoma. Br J Surg. 1986, 73: 732-735. 10.1002/bjs.1800730918.CrossRefPubMed
2.
Bathe OF, Ernst S, Sutherland FR, Dixon E, Butts C, Bigam D, Holland D, Porter GA, Koppel J, Dowden S: A phase II experience with neoadjuvant irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) for colorectal liver metastases. BMC Cancer. 2009, 9: 1-10. 10.1186/1471-2407-9-1.CrossRef
3.
Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, Curley SA, Loyer EM, Muratore A, Mentha G, Capussotti L, Vauthey JN: Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005, 241: 715-724. 10.1097/01.sla.0000160703.75808.7d.CrossRefPubMedPubMedCentral
4.
Wei AC, Greig PD, Grant D, Taylor B, Langer B, Gallinger S: Survival after hepatic resection for colorectal metastases: a 10-year experience. Ann Surg Oncol. 2006, 13: 668-676. 10.1245/ASO.2006.05.039.CrossRefPubMed
5.
Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer. Ann Surg. 1999, 230: 309-321. 10.1097/00000658-199909000-00004.CrossRefPubMedPubMedCentral
6.
Iwatsuki S, Dvorchik I, Madariaga JR, Marsh JW, Dodson F, Bonham AC, Geller DA, Gayowski TJ, Fung JJ, Starzl TE: Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system. J Am Coll Surg. 1999, 189: 291-299. 10.1016/S1072-7515(99)00089-7.CrossRefPubMedPubMedCentral
7.
Konopke R, Kersting S, Distler M, Dietrich J, Gastmeier J, Heller A, Kulisch E, Saeger HD: Prognostic factors and evaluation of a clinical score for predicting survival after resection of colorectal liver metastases. Liver Int. 2009, 29: 89-102.CrossRefPubMed
8.
Lise M, Bacchetti S, Da Pian P, Nitti D, Pilati P: Patterns of recurrence after resection of colorectal liver metastases: prediction by models of outcome analysis. World J Surg. 2001, 25: 638-644. 10.1007/s002680020138.CrossRefPubMed
9.
Minagawa M, Yamamoto J, Kosuge T, Matsuyama Y, Miyagawa S, Makuuchi M: Simplified staging system for predicting the prognosis of patients with resectable liver metastasis. Arch Surg. 2007, 142: 269-276. 10.1001/archsurg.142.3.269.CrossRefPubMed
10.
Nagashima I, Takada T, Matsuda K, Adachi M, Nagawa H, Muto T, Okinaga K: A new scoring system to classify patients with colorectal liver metastases: proposal of criteria to select candidates for hepatic resection. J Hepatobiliary Pancreat Surg. 2004, 11: 79-83. 10.1007/s00534-002-0778-7.CrossRefPubMed
11.
Rees M, Tekkis PP, Welsh FKS, O’Rourke T, John TG: Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer. Ann Surg. 2008, 247: 125-135. 10.1097/SLA.0b013e31815aa2c2.CrossRefPubMed
12.
Schindl M, Wigmore SJ, Currie EJ, Laengle F, Garden OJ: Prognostic scoring in colorectal cancer liver metastases. Arch Surg. 2005, 140: 183-189. 10.1001/archsurg.140.2.183.CrossRefPubMed
13.
Ueno H, Mochizuki H, Hatsuse K, Hase K, Yamamoto T: Indicators for treatment strategies of colorectal liver metastases. Ann Surg. 2000, 231: 59-66. 10.1097/00000658-200001000-00009.CrossRefPubMedPubMedCentral
14.
McMillan DC, Crozier JEM, Canna K, Angerson WJ, McArdle CS: Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007, 22: 881-886. 10.1007/s00384-006-0259-6.CrossRefPubMed
15.
Forrest LM, McMillan DC, McArdle CS, Anderson WJ, Dunlop DJ: Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003, 89: 1028-1030. 10.1038/sj.bjc.6601242.CrossRefPubMedPubMedCentral
16.
Ishizuka M, Nagata H, Takagi K, Horie T, Kubota K: Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer. Ann Surg. 2007, 246: 1047-1051. 10.1097/SLA.0b013e3181454171.CrossRefPubMed
17.
Roxburgh CSD, Salmond JM, Horgan PG, Oien KA, McMillan DC: Comparison of the prognostic value of inflammation-based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Ann Surg. 2009, 249: 788-793. 10.1097/SLA.0b013e3181a3e738.CrossRefPubMed
18.
Kobayashi T, Teruya M, Kishiki T, Endo D, Takenaka Y, Miki K, Kobayashi K, Morita K: Elevated c-reactive protein and hypoalbuminemia measure before resection of colorectal liver metastases predict postoperative survival. Dig Surg. 2010, 27: 285-290. 10.1159/000280021.CrossRefPubMed
19.
Wong VKH, Malik HZ, Hamady ZZR, Al-Mukhtar A, Gomez D, Prasad KR, Toogood GJ, Lodge JP: C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases. Br J Cancer. 2007, 96: 222-225. 10.1038/sj.bjc.6603558.CrossRefPubMedPubMedCentral
20.
Ishizuka M, Kita J, Shimoda M, Rokkaku K, Kato M, Sawada T, et al: Systemic inflammatory response predicts postoperative outcome in patients with liver metastases from colorectal cancer. J Surg Onc. 2009, 100: 38-42. 10.1002/jso.21294.CrossRef
21.
Malik HZ, Prasad KR, Halazun KJ, Aldoori A, Al-Mukhtar A, Gomez D, Lodge JP, Toogood GJ: Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases. Ann Surg. 2007, 246: 806-814. 10.1097/SLA.0b013e318142d964.CrossRefPubMed
22.
McMillan DC, Canna K, McArdle CS: Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg. 2003, 90: 215-219. 10.1002/bjs.4038.CrossRefPubMed
23.
Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Aoki T, Sugaya M, Miyazawa Y, Hayashi H, Miyazaki S, Ochiai T: Elevation of preoperative serum C-reactive protein level is related to poor prognosis in esophageal squamous cell carcinoma. J Surg Oncol. 2003, 83: 248-252. 10.1002/jso.10275.CrossRefPubMed
24.
Jamieson NB, Glen P, McMillan DC, McKay CJ, Foulis AK, Carter R, Imrie CW: Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas. Br J Cancer. 2005, 92: 21-23. 10.1038/sj.bjc.6602305.CrossRefPubMed
25.
Al Murri AM, Wilson C, Lannigan A, Doughty JC, Angerson WJ, McArdle CS, McMillan DC: Evaluation of the relationship between the systemic inflammatory response and cancer-specific survival in patients with primary operable breast cancer. Br J Cancer. 2007, 96: 891-895. 10.1038/sj.bjc.6603682.CrossRefPubMedPubMedCentral
26.
Hilmy M, Bartlett JMS, Underwood MA, McMillan DC: The relationship between the systemic inflammatory response and survival in patients with transitional cell carcinoma of the urinary bladder. Br J Cancer. 2005, 92: 625-627. 10.1038/sj.bjc.6602406.CrossRefPubMedPubMedCentral
27.
Hefler LA, Concin N, Hofstetter G, Marth C, Mustea A, Sehouli J, Zeillinger R, Leipold H, Lass H, Grimm C, Tempfer CB, Reinthaller A: Serum C-reactive protein as independent prognostic variable in patients with ovarian cancer. Clin Cancer Res. 2008, 14: 710-714. 10.1158/1078-0432.CCR-07-1044.CrossRefPubMed
28.
Karakiewicz PI, Hutterer GC, Trinh Q, Jeldres C, Perrotte P, Gallina A, Tostain J, Patard JJ: C-reactive protein is an informative predictor of renal cell carcinoma-specific mortality. Cancer. 2007, 110: 1241-1247. 10.1002/cncr.22896.CrossRefPubMed
29.
30.
Simon N, Friedman J, Hastie T, Tibshirani R: Regularization paths for cox’s proportional hazards model via coordinate descent. J Stat Softw. 2011, 39: 1-13.CrossRefPubMedPubMedCentral
31.
Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci. 2001, 98: 5116-5121. 10.1073/pnas.091062498.CrossRefPubMedPubMedCentral
32.
Chung YC, Chang YF: Significance of inflammatory cytokines in the progression of colorectal cancer. Hepatogastroenterology. 2003, 50: 1910-1913.PubMed
33.
Ito H, Miki C: Profile of circulating levels of interleukin-1 receptor antagonist and interleuking-6 in colorectal cancer patients. Scand J Gastroenterol. 1999, 11: 1139-1143.
34.
Knupfer H, Preiss R: Serum interleukin-6 levels in colorectal cancer patients – a summary of published results. Int J Colorectal Dis. 2010, 25: 135-140. 10.1007/s00384-009-0818-8.CrossRefPubMed
35.
Guthrie GJK, Roxburgh CSD, 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: 131-137. 10.1038/bjc.2013.291.CrossRefPubMedPubMedCentral
36.
Li A, Varney ML, Singh RK: Expression of interleukin 8 and its receptors in humon colon carcinoma cells with different metastatic potentials. Clin Cancer Res. 2001, 7: 3298-3304.PubMed
37.
Waugh DJJ, Wilson C: The interleukin-8 pathway in cancer. Clin Cancer Res. 2008, 14: 6735-6741. 10.1158/1078-0432.CCR-07-4843.CrossRefPubMed
38.
Peterson JE, Zurakowski D, Italiano JE, Michel LV, Connors S, Oenick M, D'Amato RJ, Klement GL, Folkman J: VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients. Angiogenesis. 2012, 15: 265-273. 10.1007/s10456-012-9259-z.CrossRefPubMed
39.
Cheadle EJ, Riyad K, Subar D, Rothwell DG, Ashton G, Batha H, Sherlock DJ, Hawkins RE, Gilham DE: Eotaxin-2 and colorectal cancer: a potential target for immune therapy. Clin Cancer Res. 2007, 13: 5719-5728. 10.1158/1078-0432.CCR-07-1145.CrossRefPubMed
40.
Wagsater D, Lofgren S, Hugander A, Dienus O, Dimberg J: Analysis of single nucleotide polymorphism in the promoter protein expression of the chemokine Eotaxin-1 in colorectal cancer patients. World J Surg Oncol. 2007, 5: 84-10.1186/1477-7819-5-84.CrossRefPubMedPubMedCentral
41.
Sgadari C, Angiolillo A, Cherney B, Pike SE, Farber JM, Koniaris LG, Vanguri P, Burd PR, Sheikh N, Gupta G, Teruya-Feldstein J, Tosato G: Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. Proc Natl Acad Sci. 1996, 93: 13791-13796. 10.1073/pnas.93.24.13791.CrossRefPubMedPubMedCentral
42.
Reckamp K, Figlin R, Moldawer N, Pantuck AJ, Belldegrun AS, Burdick MD, Strieter RM: Expression of CXCR3 on mononuclear cells and CXCR3 ligands in patients with metastatic renal cell carcinoma in response to systemic IL-2 therapy. J Immunother. 2007, 30: 417-424. 10.1097/CJI.0b013e31802e089a.CrossRefPubMed
43.
Jiang Z, Xu Y, Cai S: CXCL10 expression and prognostic significance in stage II and III colorectal cancer. Mol Biol Rep. 2010, 37: 3029-3036. 10.1007/s11033-009-9873-z.CrossRefPubMed
44.
Wang D, Luo H, Qiu M, Wang Z, Zhang D, Wang F, Li YH, Xu RH: Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer. Med Oncol. 2012, 29: 3092-3100. 10.1007/s12032-012-0226-8.CrossRefPubMed
45.
Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Fushiya N, Koike K, Nishino H, Tajiri H: Comparison of the prognostic value of inflammation-based prognostic scores in patients with hepatocellular carcinoma. Br J Cancer. 2012, 107: 988-993. 10.1038/bjc.2012.354.CrossRefPubMedPubMedCentral
46.
Benson AB, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, Krzyzanowska MK, Maroun J, McAllister P, Van Cutsem E, Brouwers M, Charette M, Haller DG: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004, 22: 3408-3419. 10.1200/JCO.2004.05.063.CrossRefPubMed
47.
Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, Levi F, Bismuth H: Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal liver metastases?. Ann Surg. 2004, 240: 1052-1061. 10.1097/01.sla.0000145964.08365.01.CrossRefPubMedPubMedCentral
48.
Altman DG, McShane LM, Sauerbrei W, Taube SE: Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. BMC Med. 2012, 10: 51-10.1186/1741-7015-10-51.CrossRefPubMedPubMedCentral
Metadata
Title
Identification of prognostic inflammatory factors in colorectal liver metastases
Authors
Trevor D Hamilton
Derek Leugner
Karen Kopciuk
Elijah Dixon
Francis R Sutherland
Oliver F Bathe
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-542

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Causes of death in patients with extranodal cancer of unknown primary: searching for the primary site

Research article

The inflammatory cytokine TNFα cooperates with Ras in elevating metastasis and turns WT-Ras to a tumor-promoting entity in MCF-7 cells

Research article

RETRACTED ARTICLE: STMN-1 is a potential marker of lymph node metastasis in distal esophageal adenocarcinomas and silencing its expression can reverse malignant phenotype of tumor cells

Research article

Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors

Research article

Curcumin restores sensitivity to retinoic acid in triple negative breast cancer cells

Research article

Using technology to deliver cancer follow-up: a systematic review
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits