PVALB Was Identified as an Independent Prognostic Factor for HCC Closely Related to Immunity, and Its Absence Accelerates Tumor Progression by Regulating NK Cell Infiltration

Yiyang Gong; Minqin Zhou; Yanting Zhu; Jingying Pan; Xuanrui Zhou; Yike Jiang; Hong Zeng; Hao Zheng; Xitong Geng; Da Huang

doi:10.2147/JHC.S450479

PVALB Was Identified as an Independent Prognostic Factor for HCC Closely Related to Immunity, and Its Absence Accelerates Tumor Progression by Regulating NK Cell Infiltration

J Hepatocell Carcinoma. 2024 May 8:11:813-838. doi: 10.2147/JHC.S450479. eCollection 2024.

Authors

Yiyang Gong^#^{1

2}, Minqin Zhou^#², Yanting Zhu^#², Jingying Pan², Xuanrui Zhou², Yike Jiang², Hong Zeng², Hao Zheng², Xitong Geng², Da Huang¹

Affiliations

¹ Department of Thyroid Surgery; Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
² Second College of Clinical Medicine, Nanchang University, Nanchang, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Hepatocellular carcinoma is the most common primary liver cancer, with poor prognosis. Complex immune microenvironment of the liver is linked to the development of HCC. PVALB is a calcium-binding protein which has been described as a cancer suppressor gene in thyroid cancer and glioma. Nevertheless, the role of PVALB in HCC is unknown.

Materials and methods: We obtained data from TCGA and GSE54236 datasets. MCP-counter, WGCNA and LASSO model were applied to identify PVALB. With UALCAN, MethSurv, and other websites, we probed the expression, methylation and survival of PVALB. LinkedOmics and GSEA were adopted for functional analysis, while TIMER, TISIDB, Kaplan-Meier plotter, TIDE databases were utilized to evaluate the relevance of PVALB to the tumor immune microenvironment and predict immunotherapy efficacy. TargetScan, DIANA, LncRNASNP2 databases and relevant experiments were employed to construct ceRNA network. Finally, molecular docking and drug sensitivity of PVALB were characterized by GeneMANIA, CTD, and so on.

Results: PVALB was recognized as a gene associated with HCC and NK cell. Its expression was down-regulated in HCC tissue, which lead to adverse prognosis. Besides, the hypomethylation of PVALB was related to its reduced expression. Notably, PVALB was tightly linked to immune, and its reduced expression attenuated the anticancer effect of NK cells via the Fas/FasL pathway, leading to a adverse outcome. The lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB axis may regulate the PVALB expression. Finally, we found immunotherapy might be a viable treatment option.

Conclusion: In a word, PVALB is a prognostic indicator, whose low expression facilitates HCC progression by impacting NK cell infiltration.

Keywords: PVALB; bioinformatics; ceRNA; hepatocellular carcinoma; immune; prognostic factor.

Grants and funding

This study was supported by grants from Science and Technology Project of Jiangxi Provincial Health Commission(202210611) and Science and Technology project of traditional Chinese medicine in Jiangxi province(2023Z030) and Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Plan Project (2023B1181) and Science and Natural Science Foundation of Jiang xi Province Youth Science Foundation (No:20224BAB216055) and National Natural Science Foundation of China(82260472).