Tumor Biol. DOI 10.1007/s13277-015-3723-5
RESEARCH ARTICLE
Association between mismatch repair gene and irinotecan-based chemotherapy in metastatic colon cancer Junli Ma 1 & Yan Zhang 1 & Hong Shen 2 & Linda Kapesa 1 & Wenqiang Liu 1 & Mengsi Zeng 1 & Shan Zeng 1
Received: 6 May 2015 / Accepted: 25 June 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015
Abstract Mismatch repair (MMR) gene is closely related to the pathogenesis of colon cancer. This study aimed to evaluate the association between MMR status and efficacy of irinotecan-based chemotherapy. As a target of 5-FU, thymidylate synthase (TS) expression level might be influenced by irinotecan. Understanding whether this influence of TS is related with MMR status is helpful to the further exploration of the mechanism of irinotecan sensitivity in metastatic colon cancer with different MMR status. One hundred eightyfour patients with metastatic colon cancer receiving irinotecan-based chemotherapy for the first-line treatment were included. Correlations between MMR and clinicopathological characteristics and prognosis were determined. Two pairs of colon cancer cell lines (HCT-116-hMLH1Vector (deficient MMR, dMMR) versus HCT-116-hMLH1+ (proficient MMR, pMMR); SW480-shRNA-hMLH1 (dMMR) versus SW480-shRNA-Control (pMMR)) were established by regulating MMR status. Sensitivity of these cell lines to irinotecan was determined by MTT assay. Regulation of TS by irinotecan was evaluated by western blotting and quantitative real-time PCR assay. dMMR accounted for 18.5 % and was related with proximal colon cancer (p=0.005), poorly differentiated tumors (p=0.018) and favorable efficacy with a higher disease Electronic supplementary material The online version of this article (doi:10.1007/s13277-015-3723-5) contains supplementary material, which is available to authorized users. * Shan Zeng
[email protected] 1
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
2
Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China
control rate (DCR), a longer progression-free survival (PFS) and a trend of longer overall survival (OS). dMMR colon cancer cells were more sensitive to irinotecan. TS expression level was reduced more in dMMR cells after irinotecan treatment (p53 Location Proximal Distal Differentiation Well-mod Poor-undifferentiated TS Positive Negative MMR Positive Negative ECOG 0–1 ≥2 Chemotherapy regimens Irinotecan Combined scheme
Table S2) for another 24 h, then cell viability was determined. The cell survival rates were lower in the dMMR cell lines than the pMMR cell lines (Fig. 4; p
