Expression of ERCC1 and TYMS in colorectal cancer patients and the predictive value of chemotherapy efficacy

Jiang,Hong; Li,Baosong; Wang,Fengxia; Ma,Chong; Hao,Tao

doi:10.3892/ol.2019.10395

Expression of ERCC1 and TYMS in colorectal cancer patients and the predictive value of chemotherapy efficacy

Authors:
- Hong Jiang
- Baosong Li
- Fengxia Wang
- Chong Ma
- Tao Hao
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Affiliations: Department of Colorectal and Anal Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China, Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China
Published online on: May 23, 2019 https://doi.org/10.3892/ol.2019.10395
Pages: 1157-1162
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated the expression of excision repair cross-complementing gene 1 (ERCC1) and thymidylate synthase (TYMS) in patients with colorectal cancer and the predictive value of chemotherapy. Eighty patients with colorectal cancer chemotherapy admitted to Binzhou Medical University Hospital from June 2013 to June 2015 were randomly selected, and 80 cancer tissues and 68 adjacent tissues were taken for analysis. RT-qPCR was used to detect ERCC1 as well as the expression level of TYMS. The relationship of the expression level with the chemotherapy efficacy, clinical pathology and survival time in colorectal cancer patients receiving standard chemotherapy, was compared. The expression of ERCC1 and TYMS mRNA in cancer tissues was significantly higher than that in the adjacent tissues (P<0.05). There was no correlation between ERCC1 mRNA expression, TYMS mRNA and clinicopathological features of colorectal cancer (P>0.05). The predictive effect of ERCC1 on colorectal cancer chemotherapy was 0.919 (95% CI, 0.862-0.976), P<0.001. The AUC of TYMS for predicting the efficacy of chemotherapy on colon cancer was 0.831 (95% CI, 0.735-0.926), and both had higher predictive values. The expression levels of ERCC1 and TYMS mRNA in 80 patients with colorectal cancer were divided into the low and high expression groups. The 3-year survival rate of patients in the low expression group was significantly higher than that in the high expression group, and the difference between the two groups was statistically significant (P<0.05). ERCC1 and TYMS had a high predictive value for the efficacy of chemotherapy in patients with colorectal cancer, and patients with lower expression of ERCC1 and TYMS had improved 3-year survival rates than patients with higher expression. Therefore, for patients with colorectal cancer, ERCC1 and TYMS can be used as predictors of the efficacy of chemotherapy.

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1	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI
2	Jung M, Shin SJ, Koom WS, Jung I, Keum KC, Hur H, Min BS, Baik SH, Kim NK, Kim H, et al: A randomized phase 2 study of neoadjuvant chemoradiaton therapy with 5-fluorouracil/leucovorin or irinotecan/S-1 in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 93:1015–1022. 2015. View Article : Google Scholar : PubMed/NCBI
3	Jang HJ, Kim BJ, Kim JH and Kim HS: The addition of bevacizumab in the first-line treatment for metastatic colorectal cancer: An updated meta-analysis of randomized trials. Oncotarget. 8:73009–73016. 2017. View Article : Google Scholar : PubMed/NCBI
4	Freeman K, Connock M, Cummins E, Gurung T, Taylor-Phillips S, Court R, Saunders M, Clarke A and Sutcliffe P: Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Health Technol Assess. 19:1–321, v-vi. 2015. View Article : Google Scholar
5	Li W, Jie Z, Li Z, Liu Y, Gan Q, Mao Y and Wang X: ERCC1 siRNA ameliorates drug resistance to cisplatin in gastric carcinoma cell lines. Mol Med Rep. 9:2423–2428. 2014. View Article : Google Scholar : PubMed/NCBI
6	Vilmar A and Sørensen JB: Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: A review of current literature. Lung Cancer. 64:131–139. 2009. View Article : Google Scholar : PubMed/NCBI
7	Libra M, Navolanic PM, Talamini R, Cecchin E, Sartor F, Tumolo S, Masier S, Travali S, Boiocchi M and Toffoli G: Thymidylate synthetase mRNA levels are increased in liver metastases of colorectal cancer patients resistant to fluoropyrimidine-based chemotherapy. BMC Cancer. 4:112004. View Article : Google Scholar : PubMed/NCBI
8	Wang B, Walsh SJ and Saif MW: Pancytopenia and severe gastrointestinal toxicities associated with 5-fluorouracil in a patient with thymidylate synthase (TYMS) polymorphism. Cureus. 8:e7982016.PubMed/NCBI
9	Yasumatsu R, Nakashima T, Uryu H, Ayada T, Wakasaki T, Kogo R, Masuda M, Fukushima M and Komune S: Correlations between thymidylate synthase expression and chemosensitivity to 5-fluorouracil, cell proliferation and clinical outcome in head and neck squamous cell carcinoma. Chemotherapy. 55:36–41. 2009. View Article : Google Scholar : PubMed/NCBI
10	Hu HB, Kuang L, Zeng XM, Li B, Liu EY and Zhong MZ: Predictive value of thymidylate synthase expression in gastric cancer: A systematic review with meta-analysis. Asian Pac J Cancer Prev. 13:261–267. 2012. View Article : Google Scholar : PubMed/NCBI
11	Terashima M, Irinoda T, Fujiwara H, Nakaya T, Takagane A, Abe K, Yonezawa H, Oyama K, Inaba T, Saito K, et al: Roles of thymidylate synthase and dihydropyrimidine dehydrogenase in tumor progression and sensitivity to 5-fluorouracil in human gastric cancer. Anticancer Res 22 (2A). 761–768. 2002.
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Sobrero A, Guglielmi A, Grossi F, Puglisi F and Aschele C: Mechanism of action of fluoropyrimidines: Relevance to the new developments in colorectal cancer chemotherapy. Semin Oncol. 27 (Suppl 10):72–77. 2000.PubMed/NCBI
14	Stevens EV, Nishizuka S, Antony S, Reimers M, Varma S, Young L, Munson PJ, Weinstein JN, Kohn EC and Pommier Y: Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers. Mol Cancer Ther. 7:10–18. 2008. View Article : Google Scholar : PubMed/NCBI
15	Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, Ashby MA, Dong W, Sugrue MM and Grothey A; Investigators of the BRiTE study, : Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: The BRiTE observational cohort study. Oncologist. 14:862–870. 2009. View Article : Google Scholar : PubMed/NCBI
16	Ahn SJ, Kim JH, Park SJ and Han JK: Prediction of the therapeutic response after FOLFOX and FOLFIRI treatment for patients with liver metastasis from colorectal cancer using computerized CT texture analysis. Eur J Radiol. 85:1867–1874. 2016. View Article : Google Scholar : PubMed/NCBI
17	Takenaka T, Yoshino I, Kouso H, Ohba T, Yohena T, Osoegawa A, Shoji F and Maehara Y: Combined evaluation of Rad51 and ERCC1 expressions for sensitivity to platinum agents in non-small cell lung cancer. Int J Cancer. 121:895–900. 2007. View Article : Google Scholar : PubMed/NCBI
18	Sun S, Shi W, Wu Z, Zhang G, Yang BO and Jiao S: Prognostic significance of the mRNA expression of ERCC1, RRM1, TUBB3 and TYMS genes in patients with non-small cell lung cancer. Exp Ther Med. 10:937–941. 2015. View Article : Google Scholar : PubMed/NCBI
19	Cao Y, Zhang G, Wang P, Zhou J, Gan W, Song Y, Huang L, Zhang Y, Luo G, Gong J, et al: Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer. BMC Gastroenterol. 17:22017. View Article : Google Scholar : PubMed/NCBI
20	Leng XF, Chen MW, Xian L, Dai L, Ma GY and Li MH: Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy. J Exp Clin Cancer Res. 31:252012. View Article : Google Scholar : PubMed/NCBI
21	Wei J, Zou Z, Qian X, Ding Y, Xie L, Sanchez JJ, Zhao Y, Feng J, Ling Y, Liu Y, et al: ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen. Br J Cancer. 98:1398–1402. 2008. View Article : Google Scholar : PubMed/NCBI
22	Burdelski C, Strauss C, Tsourlakis MC, Kluth M, Hube-Magg C, Melling N, Lebok P, Minner S, Koop C, Graefen M, et al: Overexpression of thymidylate synthase (TYMS) is associated with aggressive tumor features and early PSA recurrence in prostate cancer. Oncotarget. 6:8377–8387. 2015. View Article : Google Scholar : PubMed/NCBI