Prognostic signature for hepatocellular carcinoma based on 4 pyroptosis-related genes.
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ABSTRACT:
SUBMITTER: Duan S
PROVIDER: S-EPMC9336086 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Prognostic signature for hepatocellular carcinoma based on 4 pyroptosis-related genes.
Duan Sainan S Gao Jianying J Lou Weiming W Zhang Yize Y Deng Ying Y Wang Cong C Huang Haiyue H Xu Hui H Guo Sixuan S Lai Shuhui S Xi Feiyang F Li Zhangwang Z Deng Libin L Zhong Yuanbin Y
BMC medical genomics 20220728 1
<h4>Background</h4>Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis. Many recent studies have suggested that pyroptosis is important in tumour progression. However, the role of pyroptosis-related genes (PRGs) in HCC remains unclear.<h4>Materials and methods</h4>We identified differentially expressed PRGs in tumours versus normal tissues. Through univariate, LASSO, and multivariate Cox regression analyses, a prognostic PRG signature was established. The signature effectiveness was ...[more]
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Project description:Background Necroptosis is a necrotic programmed cell death with potent immunogenicity. Due to the dual effects of necroptosis on tumor growth, metastasis and immunosuppression, we evaluated the prognostic value of necroptosis-related genes (NRGs) in hepatocellular carcinoma (HCC). Methods We first analyzed RNA sequencing and clinical HCC patient data obtained to develop an NRG prognostic signature based on the TCGA dataset. Differentially expressed NRGs were further evaluated by GO and KEGG pathway analyses. Next, we conducted univariate and multivariate Cox regression analyses to build a prognostic model. We also used the dataset obtained from the International Cancer Genome Consortium (ICGC) database to verify the signature. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to investigate the immunotherapy response. Furthermore, we investigated the relationship between the prediction signature and chemotherapy treatment response in HCC. Results We first identified 36 differentially expressed genes out of 159 NRGs in hepatocellular carcinoma. Enrichment analysis showed that they were mainly enriched in the necroptosis pathway. Four NRGs were screened by Cox regression analysis to establish a prognostic model. The survival analysis revealed that the overall survival of patients with high-risk scores was significantly shorter than that of patients with low-risk scores. The nomogram demonstrated satisfactory discrimination and calibration. The calibration curves validated a fine concordance between the nomogram prediction and actual observation. The efficacy of the necroptosis-related signature was also validated by an independent dataset and immunohistochemistry experiments. TIDE analysis revealed that patients in the high-risk group were possibly more susceptible to immunotherapy. Furthermore, high-risk patients were found to be more sensitive to conventional chemotherapeutic medicines such as bleomycin, bortezomib, and imatinib. Conclusion We identified 4 necroptosis-related genes and established a prognostic risk model that could potentially predict prognosis and response to chemotherapy and immunotherapy in HCC patients in the future.
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