Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Exploring Senescence-Related Transcriptional Signatures to Uncover Molecular Subtypes and Key Genes in Hepatocellular Carcinoma

Version 1 : Received: 18 December 2023 / Approved: 19 December 2023 / Online: 19 December 2023 (12:05:10 CET)

How to cite: He, X.; Liu, F.; Xu, P.; Gong, Q. Exploring Senescence-Related Transcriptional Signatures to Uncover Molecular Subtypes and Key Genes in Hepatocellular Carcinoma. Preprints 2023, 2023121454. https://doi.org/10.20944/preprints202312.1454.v1 He, X.; Liu, F.; Xu, P.; Gong, Q. Exploring Senescence-Related Transcriptional Signatures to Uncover Molecular Subtypes and Key Genes in Hepatocellular Carcinoma. Preprints 2023, 2023121454. https://doi.org/10.20944/preprints202312.1454.v1

Abstract

Hepatocellular carcinoma (HCC) is characterized by uncontrolled cellular proliferation driven by aberrant signal transduction. Cells respond to potential carcinogenic signals by inducing cellular senescence (CS) as a defense mechanism. However, assessing CS levels in various tumors is challenging due to heterogeneity and the lack of universal CS markers. This study integrates single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from HCC samples to analyze gene expression profiles. HCC-specific senescence-related pathways are identified, and genes from these pathways distinguish molecular subtypes associated with senescence in HCC. These subtypes exhibit significant variations in biological and clinical attributes. A specific CS risk model is developed, revealing associations between CS scores and prognosis, clinical staging, immune infiltration, immunotherapy response, and drug sensitivity. The key gene G6PD is identified as a potential senescence-related target in liver cancer. Molecular experiments confirm the effective suppression of HepG2 cell proliferation, invasion, and migration upon G6PD knockdown. In summary, this analysis enhances our understanding of HCC-specific senescence molecular features and introduces a novel senescence-related biomarker, offering promising implications for future research.

Keywords

cell senescence; hepatocellular carcinoma; G6PD; molecular subtypes; immunotherapy

Subject

Medicine and Pharmacology, Urology and Nephrology

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