Development and validation of a RNA binding protein gene pair-associated prognostic signature for prediction of overall survival in hepatocellular carcinoma

Chunmiao Kang,Hongsheng Liu,Xuanhui Jia

doi:10.1186/s12938-020-00812-0

Abstract

BackgroundIncreasing evidence has demonstrated the correlation between hepatocellular carcinoma (HCC) prognosis and RNA binding proteins (RBPs) dysregulation. Thus, we aimed to develop and validate a reliable prognostic signature that can estimate the prognosis for HCC.MethodsGene expression profiling and clinical information of 374 HCC patients were derived from the TCGA data portal. The survival-related RBP pairs were determined using univariate cox-regression analysis and the signature was built based on LASSO analysis. All patients were divided patients into high-and low-risk groups according to the optimal cut off of the signature score determined by time-dependent receiver operating characteristic (ROC) curve analysis. The predictive value of the signature was further validated in an independent cohort.ResultsA 37-RBP pairs signature consisting of 61 unique genes was constructed which was significantly associated with the survival. The RBP-related signature accurately predicted the prognosis of HCC patients, and patients in high-risk groups showed poor survival in two cohorts. The novel signature was an independent prognostic factor of HCC in two cohorts (all P < 0.001). Furthermore, the C-index of the prognostic model was 0.799, which was higher than that of many established risk models. Pathway and process enrichment analysis showed that the 61 unique genes were mainly enriched in translation, ncRNA metabolic process, RNA splicing, RNA modification, and translational termination.ConclusionThe novel proposed RBP-related signature based on relative expression orderings could serve as a promising independent prognostic biomarker for patients with HCC, and could improve the individualized survival prediction in HCC.

Highlights

Increasing evidence has demonstrated the correlation between hepatocellular carcinoma (HCC) prognosis and RNA binding proteins (RBPs) dysregulation
It has reported that the incidence of HCC all over the world is highly heterogeneous owe to different risk factors, and that most HCC patients occur in South-eastern Asia and Saharan Africa, where hepatitis B virus (HBV) infection is the leading risk factor [3]
A total of 647 RBP genes were common among two datasets, and 23,353 RRGPs were constructed in two cohorts

Summary

Introduction

Increasing evidence has demonstrated the correlation between hepatocellular carcinoma (HCC) prognosis and RNA binding proteins (RBPs) dysregulation. Hepatocellular carcinoma (HCC) was the most common primary malignancy of the liver and its incidence rate is increasing [1]. Despite the rapid progress over the past few decades in earlier diagnosis and treatment of HCC, the long-term prognosis remains poor, and the 5-year survival rate remains below 20% [4]. HCC is a highly heterogeneous malignancy with substantially variable clinical outcomes, the prognoses of patients with the same TNM stage may varied due to inherent clinical and molecular diversities, and even among patients with HCC who are diagnosed as the same TNM stage and received similar clinical management, survival outcomes are various, suggesting that TNM provides incomplete prognosis information [7, 8]. Novel valid and robust prognostic signatures are indispensable to improve risk prediction and offer better information for guiding personalized therapy

Objectives

Methods

Results

Discussion

Conclusion