Abstract 2041: Microsatellite instability as a biomarker for predicting chemoradiotherapy response in rectal cancer: insights from pathological and radiomic analyses

Abstract Background: Colorectal cancer (CRC) is one of the common causes of cancer-related deaths around the world. Rectal cancer accounts for approximately 30% of all colon cancers, half of which are diagnosed as locally advanced rectal cancer. Microsatellite instability (MSI) is a key biomarker in colorectal cancer (CRC), impacting immunotherapy outcomes and potentially influencing chemoradiotherapy (CRT) responses. In this study, we investigate the correlation between treatment response to CCRT according to MSI status. Methods: Tissue specimens were obtained by preoperative biopsy from 87 patients with rectal adenocarcinoma who underwent CRT. Patients received fluorouracil-based long-course neoadjuvant therapy. MSI analysis was performed on DNA extracted from tumors and matched normal tissue. The extracted DNA was tested by PCR targeting five microsatellite loci: BAT25, BAT26, D5S346, D2S123, and D17S250. Clinical and pathological parameters, including lymphovascular invasion and T/N stage, were compared between CRT responders and non-responders. In vitro, 3 MSI-H and 6 MSS colorectal cancer cell lines underwent gradient radiation exposure. Radiosensitivity was evaluated through XTT cell viability assays and apoptotic rates quantified via flow cytometry (FACS). Results: Preoperative MSI status was observed divided into MSI (MSI-H+MSI-L) and MSS. In the responder group (n=27), there were 5 people (18.52%) with MSI and 22 people (81.48%) with MSS, and in the non-responder group (n=60), 0 (0.0%) MSI and 60 (100%) MSS were observed (P = <0.005). Additionally, there were significant differences in ypT stage (P<0.001), ypN stage (P=0.003), lymphovascular (P=0.043) and perineural invasion (P=0.035). MSI-H cell lines demonstrated greater radiosensitivity, with significantly reduced viability in XTT assays and higher apoptosis rates in FACS analysis compared to MSS cell lines. Conclusion: Our findings suggest that MSI status is a significant predictor of response to CCRT, with patients exhibiting MSI tumors showing a higher likelihood of treatment response compared to those with MSS tumors. Enhanced radiosensitivity in MSI-H cell lines further supports the predictive value of MSI testing. Future studies should confirm these findings in larger cohorts. Citation Format: Euna Jeong, Hyowon Hong, Jaemin Jo, Shin Kim, SangJun Byun, Incheol Seo, Woon Kyung Jeong, Seong Kyu Baek, Hye Won Lee. Microsatellite instability as a biomarker for predicting chemoradiotherapy response in rectal cancer: insights from pathological and radiomic analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2041.