Gene Expression Profiles Associated with Radio-Responsiveness in Locally Advanced Rectal Cancer

SIMPLE SUMMARY: Standard treatment of locally advanced rectal cancer (LARC) consists of chemotherapy, radiotherapy, and surgery. Identification of radio-resistant (RR) and radio-sensitive (RS) LARC has been a major hurdle for patient-specific treatment. The development of biomarkers that can discriminate radio-responsiveness before surgery could improve standard treatment and minimize unwanted side effects. ABSTRACT: LARC patients were sorted according to their radio-responsiveness and patient-derived organoids were established from the respective cancer tissues. Expression profiles for each group were obtained using RNA-seq. Biological and bioinformatic analysis approaches were used in deciphering genes and pathways that participate in the radio-resistance of LARC. Thirty candidate genes encoding proteins involved in radio-responsiveness–related pathways, including the immune system, DNA repair and cell-cycle control, were identified. Interestingly, one of the candidate genes, cathepsin E (CTSE), exhibited differential methylation at the promoter region that was inversely correlated with the radio-resistance of patient-derived organoids, suggesting that methylation status could contribute to radio-responsiveness. On the basis of these results, we plan to pursue development of a gene chip for diagnosing the radio-responsiveness of LARC patients, with the hope that our efforts will ultimately improve the prognosis of LARC patients.