Survival analysis of the most frequent Single Nucleotide Variants in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and its incidence is rising. The introduction of new systemic therapies, including immune-based therapies and biomarker driven therapies, has improved survival in patients at advanced stages. However, overall survival is still poor, and recent advances in understanding of the molecular alterations of HCC have not translated yet into novel biomarkers. Over the past decade, major advancements in ‘omic’ technologies have enabled monitoring of a variety of molecular and organismal processes. A comprehensive analysis of single gene mutations in HCC might lead to detect biomarkers that improve our prognosis and treatment. We developed a bioinformatics pipeline capable of analyzing genomic data to identify key regulatory molecular changes in HCC development and their influence in patient”s prognosis. By looking at genetically determined subgroups of HCC in the TCGA Liver Cancer dataset, we managed to obtain 15 genes frequently affected by oncogenic mutations and analyzed their influence in patient”s survival, identifying CSMD1 as a prognostic biomarker candidate. Nevertheless, the validation in the ICGC HCC database showed that it did not have any statistically significant influence in overall survival. This work reveals that the most frequent single gene mutations are not enough for significant survival changes in HCC and that we should focus our efforts in integrative analysis of clinical information and multi-omics to maximize our clinical benefits in this devastating disease.

Publication History

Article published online:
04 January 2021