Prognostic value of DNA repair based stratification of hepatocellular carcinoma

Abstract

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy.

A signature of 33 immune‐related gene pairs predicts clinical outcome in hepatocellular carcinoma

“…In addition, expression imbalances in certain gene pairs may play a more important role than individual differentially expressed genes. GSEA indicated that “MYC_TARGETS,” “DNA_REPAIR,” and “GLYCOLYSIS” were enriched in the high‐risk group, and these results were consistent with previous reports …”

Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

“…A recent study analyzed the prognostic impact of the expression level of DNA repair genes in HCCs (carrying the analysis in TCGA dataset and in 120 independent cases) showing the level of DNA repair genes inversely correlated with prognosis: thus, according to the level of DNA repair gene expression the HCC patients were divided into four groups [ 77 ]. Group 1 and 2, displaying the highest levels of expression of DNA reparation genes, exhibited the lowest overall survival and tumor-free survival; these two groups were characterized at molecular level by frequent mutations of TP53 and AXIN1 cluster genes [ 77 ].…”

“…A recent study analyzed the prognostic impact of the expression level of DNA repair genes in HCCs (carrying the analysis in TCGA dataset and in 120 independent cases) showing the level of DNA repair genes inversely correlated with prognosis: thus, according to the level of DNA repair gene expression the HCC patients were divided into four groups [ 77 ]. Group 1 and 2, displaying the highest levels of expression of DNA reparation genes, exhibited the lowest overall survival and tumor-free survival; these two groups were characterized at molecular level by frequent mutations of TP53 and AXIN1 cluster genes [ 77 ]. In contrast, cluster 3 and 4 of patients displayed lower levels of expression of DNA reparation genes and exhibited longer overall survival and tumor-free progression; these tumors at molecular level were characterized by low frequency of TP53 cluster gene mutations and frequent mutations of the CTNNB1 cluster genes (particularly, group 3 of HCC tumors) [ 77 ].…”

“…Group 1 and 2, displaying the highest levels of expression of DNA reparation genes, exhibited the lowest overall survival and tumor-free survival; these two groups were characterized at molecular level by frequent mutations of TP53 and AXIN1 cluster genes [ 77 ]. In contrast, cluster 3 and 4 of patients displayed lower levels of expression of DNA reparation genes and exhibited longer overall survival and tumor-free progression; these tumors at molecular level were characterized by low frequency of TP53 cluster gene mutations and frequent mutations of the CTNNB1 cluster genes (particularly, group 3 of HCC tumors) [ 77 ].…”

Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions

“…9 Dysfunction of DDR mechanisms is considered one of the main causes of MT. [10][11][12] Despite mounting evidence of a pivotal role of DDR in carcinogenesis, its investigation in PPOELs remains scarce.…”