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. 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.

Automated summary

The standard treatment for locally advanced rectal cancer (LARC) involves chemotherapy, radiotherapy, and surgery. Identifying biomarkers that can discriminate radio-responsiveness before surgery is crucial to improve treatment outcomes and reduce side effects. Research has identified candidate genes involved in radio-responsiveness, such as CTSE, which exhibited differential methylation at the promoter region inversely correlated with radio-resistance. This study aims to develop a gene chip for diagnosing radio-responsiveness in LARC patients, with the potential to improve patient prognosis.