Skip to main content
Top
Published in: Tumor Biology 4/2016

01-04-2016 | Original Article

Predictive value of blood lipid association with response to neoadjuvant chemoradiotherapy in colorectal cancer

Authors: Yan Wang, Chengxin Liu, Jianbo Zhang, Yuanyuan Liu, Guanzhong Gong, Xinkai Mo, Pei Liu, Baosheng Li, Yong Yin

Published in: Tumor Biology | Issue 4/2016

Login to get access

Abstract

The aim of this research was to explore whether blood lipid parameters could predict tumor regression grading (TRG) and compare with the predictive value of carcinoembryonic antigen (CEA) in patients with locally advanced colorectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT). Between June 2011 and January 2015, the records of 176 patients with primary colorectal adenocarcinoma treated with nCRT followed by radical surgery were reviewed retrospectively. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and pre-CEA were measured before nCRT, and post-CEA was measured before surgery. A total of 129 (73.3 %) good responders (TRG 3–4) and 47 (26.7 %) poor responders (TRG 0–2) were assessed after the nCRT. TC, LDL, HDL, and ΔCEA were 6.56 ± 0.95, 3.08 ± 0.72, and 1.43 ± 0.25 mmol/L and −0.69 ± 8.33 μg/mL in poor responders compared with 5.15 ± 1.29, 2.39 ± 0.5, and 1.37 ± 0.32 mmol/L and 16.67 ± 30.18 μg/mL in good responders, respectively (p < 0.05). TG, pre-CEA, and post-CEA were not significantly different. Multivariate logistic regression analysis revealed TC and ΔCEA as independent factors in predicting TRG; TC showed a sensitivity of 62.79 %, a specificity of 91.49 %, a Youden index of 0.543, a cutoff value of 5.52, and an AUC of 0.800 compared with ΔCEA (sensitivity 76.74 %, specificity 65.96 %, Youden index 0.427, and AUC 0.761). TC has a better predictive value than ΔCEA and hence might serve as a predictor of TRG in LARC patients.
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
2.
go back to reference Benson 3rd AB, Arnoletti JP, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, et al. Anal Carcinoma, Version 2.2012: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2012;10:449–54.PubMed Benson 3rd AB, Arnoletti JP, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, et al. Anal Carcinoma, Version 2.2012: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2012;10:449–54.PubMed
4.
go back to reference Guillem JG, Chessin DB, Cohen AM, Shia J, Mazumdar M, Enker W, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005;241:829–38.CrossRefPubMedPubMedCentral Guillem JG, Chessin DB, Cohen AM, Shia J, Mazumdar M, Enker W, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005;241:829–38.CrossRefPubMedPubMedCentral
5.
go back to reference Molinari C, Matteucci F, Caroli P, Passardi A. Biomarkers and molecular imaging as predictors of response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Clin Colorectal Cancer. 2015;05:14. Molinari C, Matteucci F, Caroli P, Passardi A. Biomarkers and molecular imaging as predictors of response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Clin Colorectal Cancer. 2015;05:14.
6.
go back to reference Kim CH, Lee SY, Kim HR, Kim YJ. Prognostic effect of pretreatment serum carcinoembryonic antigen level: a useful tool for prediction of distant metastasis in locally advanced rectal cancer following neoadjuvant chemoradiotherapy and total mesorectal excision. Medicine (Baltimore). 2015;94:31. Kim CH, Lee SY, Kim HR, Kim YJ. Prognostic effect of pretreatment serum carcinoembryonic antigen level: a useful tool for prediction of distant metastasis in locally advanced rectal cancer following neoadjuvant chemoradiotherapy and total mesorectal excision. Medicine (Baltimore). 2015;94:31.
7.
go back to reference van Duijnhoven FJ, Bueno-De-Mesquita HB, Calligaro M, Jenab M, Pischon T, Jansen EH, et al. Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition. Gut. 2011;60:1094–102.CrossRefPubMed van Duijnhoven FJ, Bueno-De-Mesquita HB, Calligaro M, Jenab M, Pischon T, Jansen EH, et al. Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition. Gut. 2011;60:1094–102.CrossRefPubMed
8.
go back to reference Kitahara CM, Berrington de González A, Freedman ND, Huxley R, Mok Y, Jee SH, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol. 2011;29:1592–8.CrossRefPubMedPubMedCentral Kitahara CM, Berrington de González A, Freedman ND, Huxley R, Mok Y, Jee SH, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol. 2011;29:1592–8.CrossRefPubMedPubMedCentral
9.
go back to reference Clendening JW, Pandyra A, Boutros PC, El Ghamrasni S, Khosravi F, Trentin GA, et al. Dysregulationof the mevalonate pathway promotes transformation. Proc Natl Acad Sci U S A. 2010;107:15051–6.CrossRefPubMedPubMedCentral Clendening JW, Pandyra A, Boutros PC, El Ghamrasni S, Khosravi F, Trentin GA, et al. Dysregulationof the mevalonate pathway promotes transformation. Proc Natl Acad Sci U S A. 2010;107:15051–6.CrossRefPubMedPubMedCentral
10.
go back to reference Kato S, Smalley S, Sadarangani A, Chen-Lin K, Oliva B, Brañes J, et al. Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase. J Cell Mol Med. 2010;14:1180–93.PubMed Kato S, Smalley S, Sadarangani A, Chen-Lin K, Oliva B, Brañes J, et al. Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase. J Cell Mol Med. 2010;14:1180–93.PubMed
11.
go back to reference Kidera Y, Tsubaki M, Yamazoe Y, Shoji K, Nakamura H, Ogaki M, et al. Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway. J Exp Clin Cancer Res. 2010;29:127.CrossRefPubMedPubMedCentral Kidera Y, Tsubaki M, Yamazoe Y, Shoji K, Nakamura H, Ogaki M, et al. Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway. J Exp Clin Cancer Res. 2010;29:127.CrossRefPubMedPubMedCentral
12.
go back to reference Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N, Ghosh Choudhury G. Simvastatin induces derepression of PTEN expression via NF kappaB to inhibit breast cancer cell growth. Cell Signal. 2010;22:749–58.CrossRefPubMedPubMedCentral Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N, Ghosh Choudhury G. Simvastatin induces derepression of PTEN expression via NF kappaB to inhibit breast cancer cell growth. Cell Signal. 2010;22:749–58.CrossRefPubMedPubMedCentral
13.
go back to reference He YS, Jin HY, Zhang JC, Zhou AC. [Experimental study of the impact of hyperlipidemia on the chemotherapy in colorectal cancer model]. Zhonghua Wei Chang Wai Ke Za Zhi. 2013;16:583–7.PubMed He YS, Jin HY, Zhang JC, Zhou AC. [Experimental study of the impact of hyperlipidemia on the chemotherapy in colorectal cancer model]. Zhonghua Wei Chang Wai Ke Za Zhi. 2013;16:583–7.PubMed
14.
go back to reference Butt S, Butt T, Jirström K, Hartman L, et al. The target for statins, HMG-CoA reductase, is expressed in ductal carcinoma-in situ and may predict patient response to radiotherapy. Ann Surg Oncol. 2014;21:2911–9.CrossRefPubMed Butt S, Butt T, Jirström K, Hartman L, et al. The target for statins, HMG-CoA reductase, is expressed in ductal carcinoma-in situ and may predict patient response to radiotherapy. Ann Surg Oncol. 2014;21:2911–9.CrossRefPubMed
15.
go back to reference Solanki AA, Liauw SL. Role of HMG-CoA reductase inhibitors with curative radiotherapy in men with prostate cancer. Open Access J Urol. 2011;3:95–104.PubMedPubMedCentral Solanki AA, Liauw SL. Role of HMG-CoA reductase inhibitors with curative radiotherapy in men with prostate cancer. Open Access J Urol. 2011;3:95–104.PubMedPubMedCentral
16.
go back to reference Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116:5336–9.CrossRefPubMed Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116:5336–9.CrossRefPubMed
17.
go back to reference Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12:19–23.CrossRefPubMed Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12:19–23.CrossRefPubMed
18.
go back to reference Huh JW, Park YA, Jung EJ, Lee KY, Sohn SK. Accuracy of endorectal ultrasonography and computed tomography for restaging rectal cancer after preoperative chemoradiation. J Am Coll Surg. 2008;207:7–12.CrossRefPubMed Huh JW, Park YA, Jung EJ, Lee KY, Sohn SK. Accuracy of endorectal ultrasonography and computed tomography for restaging rectal cancer after preoperative chemoradiation. J Am Coll Surg. 2008;207:7–12.CrossRefPubMed
19.
go back to reference Konski A, Li T, Sigurdson E, Cohen SJ, Small Jr W, Spies S, et al. Use of molecular imaging to predict clinical outcome in patients with rectal cancer after preoperative chemotherapy and radiation. Int J Radiat Oncol Biol Phys. 2009;74:55–9.CrossRefPubMed Konski A, Li T, Sigurdson E, Cohen SJ, Small Jr W, Spies S, et al. Use of molecular imaging to predict clinical outcome in patients with rectal cancer after preoperative chemotherapy and radiation. Int J Radiat Oncol Biol Phys. 2009;74:55–9.CrossRefPubMed
20.
go back to reference Kremser C, Trieb T, Rudisch A, Judmaier W, de Vries A. Dynamic T(1) mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: sequence implementation and data analysis. J Magn Reson Imaging. 2007;26:662–71.CrossRefPubMed Kremser C, Trieb T, Rudisch A, Judmaier W, de Vries A. Dynamic T(1) mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: sequence implementation and data analysis. J Magn Reson Imaging. 2007;26:662–71.CrossRefPubMed
21.
go back to reference Kim JW, Kim HC, Park JW, Park SC, Sohn DK, Choi HS, et al. Predictive value of 18FDG PET-CT for tumour response in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy. Int J Colorectal Dis. 2013;28:1217–24.CrossRefPubMed Kim JW, Kim HC, Park JW, Park SC, Sohn DK, Choi HS, et al. Predictive value of 18FDG PET-CT for tumour response in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy. Int J Colorectal Dis. 2013;28:1217–24.CrossRefPubMed
22.
go back to reference Hur H, Kim NK, Min BS, Baik SH, Lee KY, Koom WS, et al. Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer? Dis Colon Rectum. 2014;57:592–601.CrossRefPubMed Hur H, Kim NK, Min BS, Baik SH, Lee KY, Koom WS, et al. Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer? Dis Colon Rectum. 2014;57:592–601.CrossRefPubMed
23.
go back to reference Moreno García V, Cejas P, Blanco Codesido M, Feliu Batlle J, de Castro Carpeño J, Belda-Iniesta C, et al. Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy. Int J Colorectal Dis. 2009;24:741–8.CrossRefPubMed Moreno García V, Cejas P, Blanco Codesido M, Feliu Batlle J, de Castro Carpeño J, Belda-Iniesta C, et al. Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy. Int J Colorectal Dis. 2009;24:741–8.CrossRefPubMed
24.
go back to reference Meng X, Wang R, Huang Z, Zhang J, Feng R, Xu X, et al. Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: association with response to neoadjuvant therapy and prognosis. Cancer Sci. 2014;105:818–24.CrossRefPubMedPubMedCentral Meng X, Wang R, Huang Z, Zhang J, Feng R, Xu X, et al. Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: association with response to neoadjuvant therapy and prognosis. Cancer Sci. 2014;105:818–24.CrossRefPubMedPubMedCentral
25.
go back to reference Yang KL, Yang SH, Liang WY, et al. Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery. Radiat Oncol. 2013;8:43.CrossRefPubMedPubMedCentral Yang KL, Yang SH, Liang WY, et al. Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery. Radiat Oncol. 2013;8:43.CrossRefPubMedPubMedCentral
26.
go back to reference Kim CW, Yu CS, Yang SS, et al. Clinical significance of pre- to post-chemoradiotherapy s-CEA reduction ratio in rectal cancer patients treated with preoperative chemoradiotherapy and curative resection. Ann Surg Oncol. 2011;18:3271–7.CrossRefPubMed Kim CW, Yu CS, Yang SS, et al. Clinical significance of pre- to post-chemoradiotherapy s-CEA reduction ratio in rectal cancer patients treated with preoperative chemoradiotherapy and curative resection. Ann Surg Oncol. 2011;18:3271–7.CrossRefPubMed
27.
go back to reference Li C, Wang Z, Liu F, Zhu J, Yang L, Cai G, et al. CXCL10 mRNA expression predicts response to neoadjuvant chemoradiotherapy in rectal cancer patients. Tumour Biol. 2014;35:9683–91.CrossRefPubMed Li C, Wang Z, Liu F, Zhu J, Yang L, Cai G, et al. CXCL10 mRNA expression predicts response to neoadjuvant chemoradiotherapy in rectal cancer patients. Tumour Biol. 2014;35:9683–91.CrossRefPubMed
28.
go back to reference Kopecka J, Campia I, Olivero P, et al. A LDL-masked liposomal-doxorubicin reverses drug resistance in human cancer cells. J Control Release. 2011;149:196–205.CrossRefPubMed Kopecka J, Campia I, Olivero P, et al. A LDL-masked liposomal-doxorubicin reverses drug resistance in human cancer cells. J Control Release. 2011;149:196–205.CrossRefPubMed
29.
go back to reference Li YC, Park MJ, Ye SK, Kim CW, Kim YN. Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am J Pathol. 2006;168:1107e1118. Li YC, Park MJ, Ye SK, Kim CW, Kim YN. Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am J Pathol. 2006;168:1107e1118.
30.
go back to reference Riganti C, Castella B, Kopecka J, et al. Zoledronic acid restores doxorubicin chemosensitivity and immunogenic cell death in multidrug-resistant human cancer cells. PLoS One. 2013;8:e60975.CrossRefPubMedPubMedCentral Riganti C, Castella B, Kopecka J, et al. Zoledronic acid restores doxorubicin chemosensitivity and immunogenic cell death in multidrug-resistant human cancer cells. PLoS One. 2013;8:e60975.CrossRefPubMedPubMedCentral
31.
go back to reference Zhang Y, Duan G, Feng S. MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1. Biochem Biophys Res Commun. 2015;459:367–73.CrossRefPubMed Zhang Y, Duan G, Feng S. MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1. Biochem Biophys Res Commun. 2015;459:367–73.CrossRefPubMed
32.
go back to reference Connelly-Smith L, Pattinson J, Grundy M, et al. P-glycoprotein is downregulated in KG1a-primitive leukemia cells by LDL cholesterol deprivation and by HMG-CoA reductase inhibitors. Exp Hematol. 2007;35:1793–800.CrossRefPubMed Connelly-Smith L, Pattinson J, Grundy M, et al. P-glycoprotein is downregulated in KG1a-primitive leukemia cells by LDL cholesterol deprivation and by HMG-CoA reductase inhibitors. Exp Hematol. 2007;35:1793–800.CrossRefPubMed
33.
go back to reference Gelsomino G, Corsetto PA, Campia I, et al. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition. Mol Cancer. 2013;12:137.CrossRefPubMedPubMedCentral Gelsomino G, Corsetto PA, Campia I, et al. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition. Mol Cancer. 2013;12:137.CrossRefPubMedPubMedCentral
34.
go back to reference Eckford PD, Sharom FJ. Interaction of the P-glycoprotein multidrug efflux pump with cholesterol: effects on ATPase activity, drug binding and transport. Biochemistry. 2008;47:13686–98.CrossRefPubMed Eckford PD, Sharom FJ. Interaction of the P-glycoprotein multidrug efflux pump with cholesterol: effects on ATPase activity, drug binding and transport. Biochemistry. 2008;47:13686–98.CrossRefPubMed
35.
go back to reference Babcook MA, Shukla S, Fu P, et al. Synergistic simvastatin and metformin combination chemotherapy for osseous metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2014;13:2288–302.CrossRefPubMedPubMedCentral Babcook MA, Shukla S, Fu P, et al. Synergistic simvastatin and metformin combination chemotherapy for osseous metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2014;13:2288–302.CrossRefPubMedPubMedCentral
36.
go back to reference Riganti C, Voena C, Kopecka J, et al. Liposome-encapsulated doxorubicin reverses drug resistance by inhibiting P-glycoprotein in human cancer cells. Mol Pharm. 2011;8:683–700.CrossRefPubMed Riganti C, Voena C, Kopecka J, et al. Liposome-encapsulated doxorubicin reverses drug resistance by inhibiting P-glycoprotein in human cancer cells. Mol Pharm. 2011;8:683–700.CrossRefPubMed
37.
go back to reference Hamm R, Zeino M, Frewert S, et al. Up-regulation of cholesterol associated genes as novel resistance mechanism in glioblastoma cells in response to archazolid B. Toxicol Appl Pharmacol. 2014;281(1):78–86.CrossRefPubMed Hamm R, Zeino M, Frewert S, et al. Up-regulation of cholesterol associated genes as novel resistance mechanism in glioblastoma cells in response to archazolid B. Toxicol Appl Pharmacol. 2014;281(1):78–86.CrossRefPubMed
38.
go back to reference Hamm R, Chen YR, Seo EJ, et al. Induction of cholesterol biosynthesis by archazolid B in T24 bladder cancer cells. Biochem Pharmacol. 2014;91:18–30.CrossRefPubMed Hamm R, Chen YR, Seo EJ, et al. Induction of cholesterol biosynthesis by archazolid B in T24 bladder cancer cells. Biochem Pharmacol. 2014;91:18–30.CrossRefPubMed
40.
go back to reference Meyer dos Santos S, Weber CC, Franke C, et al. Cholesterol: coupling between membrane microenvironment and ABC transporter activity. Biochem Biophys Res Commun. 2007;354:216–21.CrossRefPubMed Meyer dos Santos S, Weber CC, Franke C, et al. Cholesterol: coupling between membrane microenvironment and ABC transporter activity. Biochem Biophys Res Commun. 2007;354:216–21.CrossRefPubMed
41.
go back to reference Souchek JJ, Baine MJ, Lin C, et al. Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation. Br J Cancer. 2014;111:1139–49.CrossRefPubMedPubMedCentral Souchek JJ, Baine MJ, Lin C, et al. Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation. Br J Cancer. 2014;111:1139–49.CrossRefPubMedPubMedCentral
42.
go back to reference Bionda C, Athias A, Poncet D, et al. Differential regulation of cell death in head and neck cell carcinoma through alteration of cholesterol levels in lipid rafts microdomains. Biochem Pharmacol. 2008;75:761–72.CrossRefPubMed Bionda C, Athias A, Poncet D, et al. Differential regulation of cell death in head and neck cell carcinoma through alteration of cholesterol levels in lipid rafts microdomains. Biochem Pharmacol. 2008;75:761–72.CrossRefPubMed
Metadata
Title
Predictive value of blood lipid association with response to neoadjuvant chemoradiotherapy in colorectal cancer
Authors
Yan Wang
Chengxin Liu
Jianbo Zhang
Yuanyuan Liu
Guanzhong Gong
Xinkai Mo
Pei Liu
Baosheng Li
Yong Yin
Publication date
01-04-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4320-3

Other articles of this Issue 4/2016

Tumor Biology 4/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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