XRCC2 as a predictive biomarker for radioresistance in locally advanced rectal cancer patients undergoing preoperative radiotherapy

Abstract

XRCC2 has been shown to increase the radioresistance of some cancers. Here, XRCC2 expression was investigated as a predictor of preoperative radiotherapy (PRT) treatment response in locally advanced rectal cancer (LARC). XRCC2 was found to be overexpressed in rectal cancer tissues resected from patients who underwent surgery without PRT. In addition, overall survival for LARC patients was improved in XRCC2-negative patients compared with XRCC2-positive patients after treatment with PRT (P < 0.001). XRCC2 expression was also associated with an increase in LARC radioresistance. Conversely, XRCC2-deficient cancer cells were more sensitive to irradiation in vitro, and a higher proportion of these cells underwent cell death induced by G2/M phase arrest and apoptosis. When XRCC2 was knocked down, the repair of DNA double-strand breaks caused by irradiation was impaired. Therefore, XRCC2 may increases LARC radioresistance by repairing DNA double-strand breaks and preventing cancer cell apoptosis. Moreover, the present data suggest that XRCC2 is a useful predictive biomarker of PRT treatment response in LARC patients. Thus, inhibition of XRCC2 expression or activity represents a potential therapeutic strategy for improving PRT response in LARC patients.

XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer

“…In our previous studies, we established an XRCC2-knockdown SW480 colorectal cancer cell line [29, 30]. XRCC2 expression was detected again via Western blot (Fig.…”

“…In our previous study, XRCC2 overexpression was found to inhibit colorectal cancer cell apoptosis [30]. To determine whether XRCC2-mediated chemoresistance in colorectal cancer cells is also due to inhibition of apoptosis, cell apoptosis was detected by flow cytometry.…”

“…The SW480 cell infections with human XRCC2 shRNA were performed as described previously [29, 30]. The knockdown efficiency of XRCC2 was examined by quantitative qRT-PCR and Western blot.…”

“…Cell apoptosis and cell cycle analyses by flow cytometry were performed as described previously [29, 30]. …”

“…A previously described immunofluorescence (IF) protocol was used [30]. The cells were treated with 5-FU for 24 h after they were plated into 6-well plates with slides.…”