二硫化物诱导细胞焦亡相关长链非编码RNA是预测肝细胞癌患者免疫反应和预后的潜在生物标志物。

Disulfidptosis-Associated lncRNAs are Potential Biomarkers for Predicting Immune Response and Prognosis Within Individuals Diagnosed with Hepatocellular Carcinoma.

作者信息

Wei Qian, Hou Yu-Chao, Mao Fei-Fei, Feng Jin-Kai, Wang Xu, Cheng Shu-Qun

机构信息

The First Clinical Medicine School, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China.

出版信息

Hepat Med. 2023 Dec 27;15:249-264. doi: 10.2147/HMER.S435726. eCollection 2023.

DOI:10.2147/HMER.S435726

PMID:38162389

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10757809/

Abstract

PURPOSE

Hepatocellular carcinoma (HCC) is a prevalent form of cancer that is distributed globally. Disulfidptosis, characterized by the fragility of the actin cytoskeleton, represents a distinct type of cell death and holds promise for novel cancer therapies. Nevertheless, the connection among disulfidptosis-associated long non-coding RNAs (lncRNAs) and HCC is still unexplored. This study uses an in silico approach to provide the novel biomarkers of disulfidptosis-associated lncRNAs for predicting the immune response and prognosis with HCC.

METHODS

In order to address this gap, we integrated transcriptomic data of HCC from The Cancer Genome Atlas (TCGA) and identified genes that exhibit differential expression with disulfidptosis and lncRNAs. Through co-expression analysis, we identified disulfidptosis-related lncRNAs. Afterwards, by employing univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO), a model for disulfidptosis-associated lncRNA was constructed. The risk model underwent assessment through the utilization of diverse analytical methodologies, including functional enrichment annotation, Kaplan-Meier analysis, principal component analysis (PCA), immune infiltration and immune status analysis, as well as tumor mutation analysis. Furthermore, we discussed the implications of the model in predicting drug sensitivity.

RESULTS

Our study culminated in the construction of a disulfidptosis-related lncRNA model comprising four prognostic disulfidptosis-related lncRNAs (ACYTOR, NRAV, AL080248.1, and AC069307.1). This model demonstrates exceptional diagnostic value for HCC patients and holds practical implications for guiding clinicians in personalizing immunotherapy and drug selection based on individual variations.

CONCLUSION

In summary, our research introduces a novel predictive tool utilizing disulfidptosis-related lncRNAs, offering potential guidance for the therapeutic management of HCC.

摘要

目的

肝细胞癌（HCC）是一种在全球范围内广泛分布的癌症形式。以肌动蛋白细胞骨架脆弱为特征的二硫化物诱导细胞死亡（Disulfidptosis）代表了一种独特的细胞死亡类型，为新型癌症治疗带来了希望。然而，二硫化物诱导细胞死亡相关的长链非编码RNA（lncRNAs）与HCC之间的联系仍未被探索。本研究采用计算机方法提供二硫化物诱导细胞死亡相关lncRNAs的新型生物标志物，用于预测HCC的免疫反应和预后。

方法

为了填补这一空白，我们整合了来自癌症基因组图谱（TCGA）的HCC转录组数据，并鉴定出与二硫化物诱导细胞死亡和lncRNAs表现出差异表达的基因。通过共表达分析，我们鉴定出二硫化物诱导细胞死亡相关的lncRNAs。之后，通过单变量Cox回归分析和最小绝对收缩和选择算子（LASSO），构建了一个二硫化物诱导细胞死亡相关lncRNA模型。通过使用多种分析方法对风险模型进行评估，包括功能富集注释、Kaplan-Meier分析、主成分分析（PCA）、免疫浸润和免疫状态分析以及肿瘤突变分析。此外，我们还讨论了该模型在预测药物敏感性方面的意义。