Identification of CERS5 as a novel biomarker for prognosis and immunity in hepatocellular carcinoma: a bioinformatics analysis and functional validation study

Author:

Qiu Peng1,Huang Qibo1,Feng Yunxiang1,Zhao Kai1,Shi Yuanxin1,Li Xiangyu1,Yao Wei1ORCID,Deng Zhengdong1,Wang Jianming1ORCID

Affiliation:

1. Huazhong University of Science and Technology Tongji Medical College

Abstract

Abstract Objective Hepatocellular carcinoma (HCC) is an extremely deadly cancer with few effective therapeutic options available. Ceramide synthases (CERS), a family of enzymes that regulate sphingolipid metabolism, have been suggested to play a role in cancer initiation and progression. Whereas the specific functions of CERS in HCC pathogenesis have not yet been fully elucidated. Methods The TCGA and ICGC databases were employed to analyze the expression levels and clinical relevance of CERS genes in HCC. Functional enrichment analyses were performed to identify pathways and functions associated with CERS5. The correlation between CERS5 and the tumor immune microenvironment was investigated. The mutation landscape and immunotherapy efficacy were evaluated. Functional experiments in vitro were conducted to assess CERS5’s impact on HCC cell proliferation and invasion. Results Aberrant expression of the CERS family was detected not only in HCC but also in other cancers, and has been linked to both overall survival and disease-free survival. Among the CERS family members, CERS5 was identified as the only prognosis-related gene, with up-regulated in HCC validated in the ICGC database and clinical tissue samples. Higher expression levels of CERS5 were associated with a poorer prognosis as well as an advanced pathologic stage and grade, as confirmed by the TCGA and ICGC databases. Besides, a prognostic nomogram combining pathologic stage, tumor status, and the expression of CERS5 was established and further validated, which suggested a favorable value for prognosis prediction. Functional enrichment analyses showed that the overexpression of CERS5 resulted in enriched pathways associated with carcinogenesis, drug metabolism, the PI3K/AKT/mTOR signaling pathway, and cancer immune-related pathways. In addition, the overexpression of CERS5 correlated positively with the expression of genes associated with immunogenic cell death modulators and immune checkpoints, levels of immune cell infiltration, and immunotherapy response, which was featured in an immunologically “hot” environment in the tumor microenvironment. Finally, the functional experiments showed that CERS5 knockdown has been shown to inhibit the growth and invasion of hepatocellular carcinoma, potentially through targeting the PI3K/AKT/mTOR signaling pathway. Conclusions Based on our findings, CERS5 appears to have great potential as both a precise prognostic biomarker and a novel therapeutic target in HCC.

Publisher

Research Square Platform LLC

Reference36 articles.

1. Hepatocellular carcinoma surveillance: An evidence-based approach;Harris PS;World J Gastroenterol,2019

2. Hepatocellular Carcinoma;Villanueva A;N Engl J Med,2019

3. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;Sung H;CA Cancer J Clin,2021

4. Singal AG, Kudo M, Bruix J. Breakthroughs in Hepatocellular Carcinoma Therapies. Clin Gastroenterol Hepatol; 2023.

5. Immunotherapy for hepatocellular carcinoma: Recent advances and future targets;Yu SJ;Pharmacol Ther,2023

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3