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The development and validation of a novel senescence-related long-chain non-coding RNA (lncRNA) signature that predicts prognosis and the tumor microenvironment of patients with hepatocellular carcinoma

Authors :
Enmin Huang
Tao Ma
Junyi Zhou
Ning Ma
Weisheng Yang
Chuangxiong Liu
Zehui Hou
Shuang Chen
Tiago Biachi de Castria
Bing Zeng
Zhen Zong
Taicheng Zhou
Source :
Annals of translational medicine. 10(14)
Publication Year :
2022

Abstract

The epigenetic regulators of cellular senescence, especially long non-coding RNAs (lncRNAs), remain unclear. The expression levels of lncRNA were previously known to be prognostic indicators for tumors. We hypothesized that lncRNAs regulating cellular senescence could also predict prognosis in patients with hepatocellular carcinoma (HCC) and developed a novel lncRNA predictive signature.Using RNA sequencing data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database, a co-expression network of senescence-related messenger RNAs (mRNAs) and lncRNAs was constructed. Using univariate Cox regression analysis and a stepwise multiple Cox regression analysis, we constructed a prognostic HCC senescence-related lncRNA signature (HCCSenLncSig). Kaplan-Meier analysis was used to compare the overall survival (OS) of high- and low-risk groups stratified by the HCCSenLncSig. Furthermore, the HCCSenLncSig risk score and other clinical characteristics were included to develop an HCC prognostic nomogram. The accuracy of the model was evaluated by the time dependent receiver operating characteristic (ROC) and calibration curves, respectively.We obtained a prognostic risk model consisting of 8 senescence-related lncRNAs: AL117336.3, AC103760.1, FOXD2-AS1, AC009283.1, AC026401.3, AC021491.4, AC124067.4, and RHPN1-AS1. The HCCSenLncSig high-risk group was associated with poor OS [hazard ratio (HR) =1.125, 95% confidence interval (CI): 1.082-1.169; P0.001]. The accuracy of the model was further supported by ROC curves (the area under the curve is 0.783, sensitivity of 0.600, and specificity of 0.896 at the cut-off value of 1.447). The HCCSenLncSig was found to be an independent prognostic factor from other clinical factors in both univariate and multivariate Cox regression analyses. The prognostic nomogram shows HCCSenLncSig has a good prognostic effect for survival risk stratification. Finally, we found that a higher number of immunosuppressed Treg cells infiltrate in high-risk patients (P0.001 compared to low-risk patients), possibly explaining why these patients have a poor prognosis. On the other hand, the expression of immunotherapy markers, such as CD276, PDCD1, and CTLA4, was also up-regulated in the high-risk patients, indicating potential immunotherapy response in these patients.The development of HCCSenLncSig allows us to better predict HCC patients' survival outcomes and disease risk, as well as contribute to the development of novel HCC anti-cancer therapeutic strategies.

Subjects

Subjects :
General Medicine

Details

ISSN :
23055839
Volume :
10
Issue :
14
Database :
OpenAIRE
Journal :
Annals of translational medicine
Accession number :
edsair.doi.dedup.....eb4f49f6bdf37f2eaa17a0f8579382f9