A pyroptosis-related gene signature provides an alternative for predicting the prognosis of patients with hepatocellular carcinoma

BMC Medical Genomics

Research

Xiaohong Zhu¹  Yinrong Ding²  Fujun Yu²  Zhuoyan Chen²  Qian Xu²  Yuan Zeng²  Luying Zhao²  Xian Song²  Dezhao Lin³ 

[1] Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, Zhejiang, People’s Republic of China;Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, Zhejiang, People’s Republic of China;Department of Surgical Oncology, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China;

关键词: Hepatocellular carcinoma (HCC);    Pyroptosis;    Gene signature;    Overall survival;    Immune status;    Drug sensitivity;   

DOI  :  10.1186/s12920-023-01431-z

 received in 2022-09-24, accepted in 2023-01-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHepatocellular Carcinoma (HCC) is a common malignant neoplasm with limited treatment options and poor outcomes. Thus, there is an urgent need to find sensitive biomarkers for HCC.MethodsGene expression and clinicopathological information were obtained from public databases, based on which a pyroptosis-related gene signature was constructed by the least absolute shrinkage and selection operator Cox regression. The applicability of the signature was evaluated via Kaplan–Meier curve and time-dependent ROC curve. TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT, ssGSEA, and ESTIMATE were employed to assess the immune status. Comparisons between groups were analyzed with Wilcoxon test. Pearson and Spearman correlation analyses were adopted for linear correlation analysis. Genetic knockdown was conducted using siRNA transfection and the mRNA expression levels of interest genes were measured using quantitative reverse transcription PCR. Finally, protein levels in 10 paired tumor tissues and adjacent non-tumor tissues from HCC patients were measured using immunohistochemistry.ResultsA pyroptosis-related gene signature was established successfully to calculate independent prognostic risk scores. It was found that survival outcomes varied significantly between different risk groups. In addition, an attenuated antitumor immune response was found in the high-risk group. Meanwhile, multiple immune checkpoints were up-regulated in high-risk score patients. Cell cycle-related genes, angiogenesis-related genes and tumor drug resistance genes were also markedly elevated. Knockdown of prognostic genes in the signature significantly inhibited the expression of immune checkpoint genes and angiogenesis-related genes. Besides, each prognostic gene was expressed at a higher level in HCC tissues than in adjacent normal tissues.ConclusionsWe successfully established a novel pyroptosis-related gene signature which could help predict the overall survival and assess the immune status of HCC patients.

【 授权许可】

CC BY   
© The Author(s) 2023

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