Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC), the primary hepatic malignancy, represents the second-highest cause of cancer-related death worldwide. Many efforts have been devoted to finding novel biomarkers for predicting both patients’ survival and the outcome of pharmacological treatments, with a particular focus on immunotherapy. In this regard, recent studies have focused on unravelling the role of tumor mutational burden (TMB), i.e., the total number of mutations per coding area of a tumor genome, to ascertain whether it can be considered a reliable biomarker to be used either for the stratification of HCC patients in subgroups with different responsiveness to immunotherapy, or for the prediction of disease progression, particularly in relation to the different HCC etiologies. In this review, we summarize the recent advances on the study of TMB and TMB-related biomarkers in the HCC landscape, focusing on their feasibility as guides for therapy decisions and/or predictors of clinical outcome.

The development of prognostic gene markers associated with disulfidptosis in gastric cancer and their application in predicting drug response

“…6 F). TMB serves as an indicator of mutation counts in cancer [ 22 ]. A higher TMB increases self-neoantigens and immunogenic recognition, enhancing the likelihood of T cell recognition, facilitating T cell responses against tumor cells, and indicating improved outcomes with ICI [ 23 ].…”

Prognostic and immune predictive roles of a novel tricarboxylic acid cycle-based model in hepatocellular carcinoma

“…4 F). Mutations associated with detrimental biological behavior were more abundant in the high-risk group than in the low-risk group, such as TP53 (36% vs. 24%), a well-known anti-oncogene that is one of the most frequently mutated genes in HCC specimens, and DOCK2 (9% vs. 3%), a mediator of cytokinesis 21 . According to the genomic characteristics of HCC mutations obtained from the previous study, we noted significant differences in the aspects of SNV neoantigens, fraction altered, aneuploidy score, and homologous recombination defects between the two groups (Fig.…”

Advances in Immunotherapy for Hepatocellular Carcinoma (HCC)

“…Research has shown that a high TMB has been associated with a better ICI response in several solid tumor types [93][94][95]. However, this association is not consistent in HCC [96].…”