Prognostic value and potential mechanism of cellular senescence and tumor microenvironment in hepatocellular carcinoma: Insights from bulk transcriptomics and single-cell sequencing analysis
机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Gen Surg, Beijing, Peoples R China首都医科大学宣武医院[2]Capital Med Univ, Clin Ctr Acute Pancreatitis, Beijing, Peoples R China[3]Peking Univ First Hosp, Dept Thyroid & Breast Surg, Beijing, Peoples R China[4]Capital Med Univ, Xuanwu Hosp, Dept Gen Surg, Beijing 100053, Peoples R China首都医科大学宣武医院
The high mortality rate and postoperative recurrence of hepatocellular carcinoma (HCC) contribute to the burden on society and healthcare. The prognostic value and underlying mechanisms of cellular senescence and tumor microenvironment (TME) in HCC remain unclear. Bulk transcriptomic data were obtained from 368 HCC samples in The Cancer Genome Atlas-liver hepatocellular carcinoma cohort and 64 samples from the GSE116174 dataset. Single-cell RNA sequencing (scRNA-seq) data of HCC were obtained from the GSE149614 dataset, including 18 tumor samples from 10 patients. Prognosis-related cellular senescence genes and immune cells were identified through univariate analysis. Least absolute shrinkage and selection operator regression analysis was performed to construct the CellAge score and TME score, both of which were identified as independent prognostic factors for HCC based on multivariate Cox analysis. The combined CellAge and TME scores showed improved prognostic stratification for HCC patients, as confirmed by multivariate Cox analysis (p < .001). The gene set enrichment analysis (GSEA) revealed enrichment of the extracellular matrix receptor interaction signaling pathway in the group with high CellAge scores and low TME scores, which exhibited a worse prognosis. Single-cell sequencing results revealed higher expression activity of the cAMP response element modulator (CREM) extended transcription factor in HCC cells and most immune cells, indicating its involvement in TME remodeling. Finally, the tumor immune dysfunction and exclusion (TIDE) analysis demonstrated that the combined scores could predict the outcomes of immune therapy in patients with HCC. In conclusion, cellular senescence contributes to TME remodeling in HCC, and the developed CellAge and TME scores serve as independent prognostic factors and predictors of immune therapy in HCC.
基金:
Beijing Municipal Science and Technology
Commission Clinical Diagnosis and Treatment
Technology Research and Demonstration
Application Project, Grant/Award Number:
Z191100006619038; Construction Project of
Clinical Advanced subjects of Capital Medical
University, Grant/Award Number:
1192070312; Capital Medical Development
and Research Special Project, Grant/Award
Number: Z201100005520090
第一作者机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Gen Surg, Beijing, Peoples R China[2]Capital Med Univ, Clin Ctr Acute Pancreatitis, Beijing, Peoples R China
通讯作者:
通讯机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Gen Surg, Beijing, Peoples R China[2]Capital Med Univ, Clin Ctr Acute Pancreatitis, Beijing, Peoples R China[4]Capital Med Univ, Xuanwu Hosp, Dept Gen Surg, Beijing 100053, Peoples R China
推荐引用方式(GB/T 7714):
Qu Chang,Wu Qian,Lu Jiongdi,et al.Prognostic value and potential mechanism of cellular senescence and tumor microenvironment in hepatocellular carcinoma: Insights from bulk transcriptomics and single-cell sequencing analysis[J].ENVIRONMENTAL TOXICOLOGY.2024,39(5):2512-2527.doi:10.1002/tox.24121.
APA:
Qu, Chang,Wu, Qian,Lu, Jiongdi&Li, Fei.(2024).Prognostic value and potential mechanism of cellular senescence and tumor microenvironment in hepatocellular carcinoma: Insights from bulk transcriptomics and single-cell sequencing analysis.ENVIRONMENTAL TOXICOLOGY,39,(5)
MLA:
Qu, Chang,et al."Prognostic value and potential mechanism of cellular senescence and tumor microenvironment in hepatocellular carcinoma: Insights from bulk transcriptomics and single-cell sequencing analysis".ENVIRONMENTAL TOXICOLOGY 39..5(2024):2512-2527