The role of double‐strand break repair, translesion synthesis, and interstrand crosslinks in colorectal cancer progression—clinicopathological data and survival

Abstract

Background and Objectives DNA repair is a new and important pathway that explains colorectal carcinogenesis. This study will evaluate the prognostic value of molecular modulation of double‐strand break repair (XRCC2 and XRCC5); DNA damage tolerance/translesion synthesis (POLH, POLK, and POLQ), and interstrand crosslink repair (DCLRE1A) in sporadic colorectal cancer (CRC). Methods Tumor specimens and matched healthy mucosal tissues from 47 patients with CRC who underwent surgery were assessed for gene expression of XRCC2, XRCC5, POLH, POLK, POLQ, and DCLRE1A; protein expression of Polk, Ku80, p53, Ki67, and mismatch repair MLH1 and MSH2 components; CpG island promoter methylation of XRCC5, POLH, POLK, POLQ, and DCLRE1A was performed. Results Neoplastic tissues exhibited induction of POLK (P < .001) and DCLRE1A (P < .001) expression and low expression of POLH (P < .001) and POLQ (P < .001) in comparison to healthy paired mucosa. Low expression of POLH was associated with mucinous histology and T1‐T2 tumors (P = .038); low tumor expression of POLK was associated with distant metastases (P = .042). CRC harboring POLK promoter methylation exhibited better disease‐free survival (DFS) (P = .005). Conclusions This study demonstrated that low expression or unmethylated POLH and POLK were related to worse biological behavior tumors. However, POLK methylation was associated with better DFS. POLK and POLH are potential prognostic biomarkers in CRC.

Boris knockout eliminates AOM/DSS‐induced in situ colorectal cancer by suppressing DNA damage repair and inflammation

“…However, there was less phospho‐γH2AX in the WT tissue than in the negative control (Figure 5A). Our results demonstrated that Boris enhances DNA repair under the treatment of AOM and DSS 23,24 . Therefore, 12 genes responsible for DNA damage repair were examined.…”

“…Our results demonstrated that Boris enhances DNA repair under the treatment of AOM and DSS. 23 , 24 Therefore, 12 genes responsible for DNA damage repair were examined. Three genes, MYC , BRCA1 , and POLH , were significantly downregulated after Boris knockout compared with the WT control (Figure 5B–E ).…”

High-Throughput Mass Spectrometry Analysis of N-Glycans and Protein Markers after FUT8 Knockdown in the Syngeneic SW480/SW620 Colorectal Cancer Cell Model

“…These results indicate that the inhibition of XRCC5 or XRCC6 improves the effectiveness of chemotherapy used in CRC, such as platinum-based drugs and/or radiotherapy. However, the downregulation of XRCC5 or XRCC6 is also associated with a poorer outcome of CRC; , one possible explanation is the intracellular localization of these proteins. In this regard, SW480 and SW620 cells manifest opposite responses to radiotherapy: the former is radioresistant and the latter is radiosensitive .…”

CENPO regulated proliferation and apoptosis of colorectal cancer in a p53-dependent manner

“…Colorectal cancer (CRC) is the third most common cancer in the world, and the proportion of women is slightly higher than that of men [ 1 ]. As with other types of cancer, mutations in certain genes, such as oncogenes and tumor suppressor genes, may contribute to the development of CRC [ 2 ]. CRC can be divided into sporadic, hereditary and familial based on the different pathways of mutations such as chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylation phenotype (CIMP) [ 3 – 5 ].…”