YBX1 as a prognostic biomarker and potential therapeutic target in hepatocellular carcinoma: A comprehensive investigation through bioinformatics analysis and in vitro study

Zizhen Li; Wenhua Lu; Feng Yin; Amin Huang

doi:10.1016/j.tranon.2024.101965

YBX1 as a prognostic biomarker and potential therapeutic target in hepatocellular carcinoma: A comprehensive investigation through bioinformatics analysis and in vitro study

Transl Oncol. 2024 Apr 29:45:101965. doi: 10.1016/j.tranon.2024.101965. Online ahead of print.

Authors

Zizhen Li¹, Wenhua Lu², Feng Yin², Amin Huang³

Affiliations

¹ Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510000, China.
² State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou 510000, China.
³ Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510000, China. Electronic address: huangam3@mail.sysu.edu.cn.

Abstract

Backgrounds: Y-box binding protein 1 (YBX1) is a DNA/RNA binding protein known to contribute to the progression of various malignancies, however, a comprehensive pan-cancer analysis to investigate YBX1 across a broad spectrum of cancer types has not yet been conducted.

Methods: We utilized the TIMER database for a comprehensive pan-cancer analysis and assessed YBX-1 expression via the TCGA and GEO databases. The relationship between YBX-1 expression and tumor-infiltrating cells was examined using TIMER and the R programming language. To evaluate the prognostic value of YBX1, we performed Kaplan-Meier plots and Cox regression analyses. Through LinkedOmics, we identified genes significantly correlated with YBX-1. The WEB-based Gene SeT AnaLysis Toolkit was used for KEGG pathway enrichment analysis. Additionally, using shRNA-mediated knockdown, we explored the potential role of YBX1 in tumor cell biology.

Results: Our study identifies pronounced overexpression of YBX-1 across multiple cancer types, correlating with adverse outcomes, notably in liver hepatocellular carcinoma (LIHC). A distinct association between elevated YBX-1 expression and heightened immune cell infiltration suggests YBX-1's potential role in reshaping the tumor microenvironment. Intriguingly, our KEGG pathway analysis indicated a tight nexus between YBX-1 expression and lipid metabolism. Moreover, the suppression of YBX-1 via shRNA revealed diminished cellular proliferation and marked reductions in crucial molecules steering the fatty acid synthesis pathway, implicating YBX-1's potential regulatory role in lipid metabolism within LIHC.

Conclusions: YBX-1 serves as a favorable prognostic indicator in various cancers, particularly in liver hepatocellular carcinoma. Targeting YBX1 in HCC offers potential therapeutic strategies. This work paves the way for fresh insights into targeted therapeutic approaches for cancers, especially benefiting liver hepatocellular carcinoma patients.

Keywords: Fatty acid metabolism; Liver hepatocellular carcinoma; Pan cancer; YBX1.