%0 Journal Article
%T Identification of DNA Repair-related Genes as Biomarkers Reflecting MSI, TMB, and TIL in Colorectal Cancer.
%A Fukuda J
%A Sudo T
%A Kikuchi M
%A Kawahara A
%A Shigyo H
%A Kawamoto Y
%A Shimamura S
%A Koga F
%A Noguchi T
%A Nakane H
%A Shigaki T
%A Fujiyoshi K
%A Yomoda T
%A Yoshida N
%A Koushi K
%A Yoshida T
%A Akiba J
%A Fujita F
%J Anticancer Res
%V 44
%N 8
%D 2024 Aug
%M 39060055
%F 2.435
%R 10.21873/anticanres.17179
%X <B>OBJECTIVE: </B>There are no established biomarkers for immune checkpoint inhibitors (ICI) in colorectal cancer (CRC) with microsatellite stability (MSS) or proficient mismatch repair (pMMR). Therefore, this study aimed to identify biomarkers for ICI benefit in patients with pMMR by analyzing the down-regulated DNA repair-related genes involved in highly immunogenic and immune responses, and comparing their expression levels and clinical features.<BR><B>METHODS: </B>Mismatch repair (MMR), tumor-infiltrating lymphocytes (TIL), and tumor mutation burden (TMB) were evaluated in 13 CRC cases and mRNA expression levels of 95 DNA repair-related genes were measured. DNA repair-related genes with reduced mRNA expression in the high immunogenicity and high immune response groups were identified. Then, the mRNA expression levels of the identified DNA repair-related genes were measured in 135 patients with CRC. Hierarchical cluster analysis was performed using the mRNA expression levels to compare the clinicopathological characteristics of each cluster.<BR><B>RESULTS: </B>ATR, LIG4, and RAD52 mRNA levels were significantly down-regulated in the high immunogenicity group. GADD45B, SMUG1, and XRCC6 mRNA levels were significantly down-regulated in the high immune response group. Cases in the cluster with reduced mRNA expression of the six genes were pMMR cases. CD8 mRNA expression level was higher in this cluster than in the other clusters.<BR><B>CONCLUSIONS: </B>Decreased mRNA expression levels of ATR, LIG4, RAD52, GADD45B, SMUG1, and XRCC6 genes were associated with high cytotoxic T cell and TMB levels, suggesting that these genes could serve as biomarkers for ICI efficacy in pMMR cases.