PMID- 32266127 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 10 DP - 2020 TI - The Predictive Value of Estrogen Receptor 1 on Adjuvant Chemotherapy in Locally Advanced Colorectal Cancer: A Retrospective Analysis With Independent Validation and Its Potential Mechanism. PG - 214 LID - 10.3389/fonc.2020.00214 [doi] LID - 214 AB - Purpose: To investigate the predictive biomarker value of estrogen receptor 1 (ESR1) expression in tumor tissue on adjuvant chemotherapy in curatively resected colorectal cancer (CRC). Methods: A total of 467 CRC patients in 2007-2010 were retrospectively evaluated. Clinical information and follow-up data were retrieved from hospital registries and patient files. What's more, we used an external independent cohort (n = 511) from GSE39582 for further validation. Overall survival was estimated by the Kaplan-Meier method, and the survival curves were compared by log-rank tests. Cox proportional hazards models were used for multivariate analyses to calculate the hazard ratios (HRs) and test independent significance. Immunohistochemistry and Western blot were applied to detect protein expression of ESR1 in CRC patients and cell lines. The stable knockdown and overexpressed cells were transduced with the lentivirus. Cell viability was measured by an MTS reagent. Results: The predictive value of ESR1 was investigated in locally advanced CRC patients. Kaplan-Meier analysis indicated that ESR1 expression was significantly correlated with OS in patients receiving adjuvant chemotherapy from these cohorts, with p = 0.015 and p < 0.001, respectively. ESR1 expression was significantly correlated with 5-flurouracil (5-FU)-based adjuvant chemotherapy in training with an HR of 1.792 (95%CI: 1.100-2.921, p = 0.019). Downregulation of ESR1 was related with enhanced chemosensitivity to 5-FU in CRC cell lines, while upregulation of ESR1 was correlated with decreased chemosensitivity. Conclusions: The present study manifest clinical validity of ESR1 expression as a predictive biomarker on 5-FU-based adjuvant chemotherapy in stage II-III CRC. CI - Copyright (c) 2020 Ye, Cheng, Deng, Deng, Li, Zhang and Lan. FAU - Ye, Shu-Biao AU - Ye SB AD - Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Cheng, Yi-Kan AU - Cheng YK AD - Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Radiation Oncology, Guangdong Institute of Gastroenterology, Guangzhou, China. FAU - Deng, Ru AU - Deng R AD - Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Oncology, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Deng, Yanhong AU - Deng Y AD - Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Oncology, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Li, Peisi AU - Li P AD - School of Medicine, Sun Yat-sen University, Guangzhou, China. FAU - Zhang, Lin AU - Zhang L AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Lan, Ping AU - Lan P AD - Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. LA - eng PT - Journal Article DEP - 20200320 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC7100261 OTO - NOTNLM OT - ESR1 OT - adjuvant chemotherapy OT - colorectal cancer OT - predictive OT - retrospective analysis EDAT- 2020/04/09 06:00 MHDA- 2020/04/09 06:01 PMCR- 2020/01/01 CRDT- 2020/04/09 06:00 PHST- 2019/11/14 00:00 [received] PHST- 2020/02/07 00:00 [accepted] PHST- 2020/04/09 06:00 [entrez] PHST- 2020/04/09 06:00 [pubmed] PHST- 2020/04/09 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2020.00214 [doi] PST - epublish SO - Front Oncol. 2020 Mar 20;10:214. doi: 10.3389/fonc.2020.00214. eCollection 2020.