3:27 PM Abstract No. 193 Identification of mRNA-encoded prognostic biomarkers for hepatocellular carcinoma

Abstract

Hepatocellular Carcinoma (HCC) has become the fastest growing lethal cancer in the United States. Current selection of a specific locoregional treatment for HCC is based on imaging findings and operator experience. There remains a clear lack of reliable objective criteria for selection of an appropriate loco regional treatment. Non-invasive serological biomarkers combined with imaging techniques can be a valuable tool for determining appropriate locoregional therapies. The purpose of this study is to identify mRNA encoded prognostic biomarkers for precision treatment and outcome prediction. We have studied mRNA expression and overall survival (OS) of 364 HCC patients downloaded from The Cancer Genome Atlas (TCGA) using the Kaplan-Meier plotter database (1). The cohorts of patients’ OS were analyzed by multivariate analysis. Hazard ratio, false discovery rate, and log rank P values were subsequently determined. A P value < 0.01 was considered statistically significant. Transcriptome of those selected mRNAs in HCC tissues were analyzed by RNA-seq. Validation of those mRNA encoded proteins were performed using patients’ plasma by ELISA assays. High mRNA expression of ANXA2, FUBP1 and CDK1 are significantly correlated with lower OS, whereas high mRNA expression of KNG1 and CD274 and TRIM72 were associated with higher OS in all combined stages. RNA-seq analysis for transcriptome indicated only ANXA2, FUBP1, CDK1 and KNG1 are prognostic for liver cancer survival. High expression of ANXA2, FUBP1, CDK1 are unfavorable, whereas high expression of KNG1 is favorable for liver cancer survival. Analysis of those mRNA encoded proteins in patients’ plasma demonstrated high level of Annexin A2, but low level of Kininogen 1 expression in liver cancer patients comparing to healthy donors. This study identified a panel of 4 mRNA molecules (ANXA2, FUBP1, CDK1 and KNG1) and their encoded proteins which can be used as potential prognostic biomarkers for HCC patients. Future studies with a larger sample size are needed to validate our findings. Applications of those prognostic biomarkers will improve precision treatment and outcome prediction of hepatocellular carcinoma.