Development and validation of LRP1B mutation-associated prognostic model for hepatocellular carcinoma.

Jian Xu,Xiaomin Shen,Mingxuan Cui,Bo Zhang,Rui Su,Lihua Yan,Yu Cao

doi:10.1042/bsr20211053

Abstract

Purpose: To develop a lipoprotein receptor-related protein 1B (LRP1B) gene mutation-based prognostic model for hepatocellular carcinoma (HCC) patients risk prediction. Methods: The LRP1B gene mutation rate was calculated from HCC patient samples. Meanwhile, differentially expressed genes according to LRP1B mutant were screened out for prognostic model establishment. Based on this innovative model, HCC patients were categorized into high- and low-risk groups. The immune status including immune cell infiltration ratio and checkpoints have been explored in two groups. The functions of LRP1B and risk factors in the model were verified using both in vivo and in vitro experiments. Results: It could be demonstrated that LRP1B was a potential negative predictor for HCC patients prognosis with high mutation frequency. The functions of LRP1B were verified with ELISA and Quantitative Real-time PCR method based on clinic-recruited HCC participants. Eleven genes displayed significant differences according to LRP1B status, which could better predict HCC patient prognosis. The functions of these genes were examined using HCC cell line HCCLM3, suggesting they played a pivotal role in determining HCC cell proliferation and apoptosis. From the immune cell infiltration ratio analysis, there was a significant difference in the infiltration degree of seven types of immune cells and two immune checkpoints between high- and low-risk HCC patients. Conclusion: The present study hypothesized a potential prognostic biomarker and developed a novel LRP1B mutation-associated prognostic model for HCC, which provided a systematic reference for future understanding of clinical research.

Highlights

Hepatocellular carcinoma (HCC) is the fourth most abundant malignant tumor in the world as well as the second leading cause for the cancer-related human deaths, accounting for nearly 841000 new cases and 782000 deaths annually [1]
The mutation rate of lipoprotein receptor-related protein 1B (LRP1B) gene was high in The Cancer Genome Atlas (TCGA) patients with HCC, ranking at the 13th place, reaching ∼8% (Figure 1A), and the overall survival (OS) of LRP1B mutant HCC patients was significantly lower than that of LRP1B wildtype HCC patients (Figure 1B)
To confirm this in clinic, we examined the concentration of LRP1B using ELISA method

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fourth most abundant malignant tumor in the world as well as the second leading cause for the cancer-related human deaths, accounting for nearly 841000 new cases and 782000 deaths annually [1]. In the aspect of virus infection, the hepatitis B virus (HBV) and hepatitis C virus (HCV) are the critical causes for HCC development [2]. In addition to the viral hepatitis from HBV and HCV, there are still some non-viral risk factors that can induce the development of HCC [3]. Alcohol abuse, cardiovascular disease, liver inflammation, obesity, dyslipidemia and non-alcoholic fatty liver disease (NAFLD) are some other major contributors to HCC development [4,5,6]. The prospects for better diagnosis and treatments of HCC have dramatically improved over the past decade, a comprehensive understanding of the pathogenesis of HCC remains a substantial impediment.

Methods

Results

Conclusion