A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility.

A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility.
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肝细胞癌中与二硫键合酶相关的lncRNAs特征:预后预测、肿瘤免疫微环境和药物敏感性

DOI:
10.1038/s41598-024-51459-z
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发表时间:
2024-01-07
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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双曲下垂是一种新型的程序性细胞死亡,近年来引起了国内外研究者的广泛关注。然而,二硫中毒相关lncRNAs (drl)在肝细胞癌(LIHC)中的作用尚未得到研究。我们的目的是建立和验证drl的预后特征,并分析LIHC患者的肿瘤微环境(TME)和药物敏感性。RNA测序数据、突变数据和临床数据均来自癌症基因组图谱数据库(TCGA)。采用Lasso算法和cox回归分析确定预后drl特征。Kaplan-Meier曲线、主成分分析(PCA)、nomogram and calibration curve、功能富集、TME、免疫功能障碍和排斥(TIDE)、肿瘤突变负担(TMB)、药物敏感性分析等。使用外部数据集验证drl的预测价值。qRT-PCR还用于验证目标lncrna在组织样本和细胞系中的差异表达。我们建立了LIHC中drl (MKLN1-AS和TMCC1-AS1)的预后特征。该特征可以将LIHC患者分为低危组和高危组,高危组与较差的预后相关。我们观察到两个危险组之间肿瘤浸润免疫细胞、免疫功能、功能富集和TIDE的差异。高危组LIHC患者对几种化疗药物更敏感。外部数据集、临床组织和细胞系证实,MKLN1-AS和TMCC1-AS1的表达在LIHC中上调,并与较差的预后相关。基于两种drl的新特征为LIHC的预后预测、TME和潜在的治疗策略提供了新的见解。
Disulfidptosis, a novel type of programmed cell death, has attracted researchers’ attention worldwide. However, the role of disulfidptosis-related lncRNAs (DRLs) in liver hepatocellular carcinoma (LIHC) not yet been studied. We aimed to establish and validate a prognostic signature of DRLs and analyze tumor microenvironment (TME) and drug susceptibility in LIHC patients. RNA sequencing data, mutation data, and clinical data were obtained from the Cancer Genome Atlas Database (TCGA). Lasso algorithm and cox regression analysis were performed to identify a prognostic DRLs signature. Kaplan–Meier curves, principal component analysis (PCA), nomogram and calibration curve, function enrichment, TME, immune dysfunction and exclusion (TIDE), tumor mutation burden (TMB), and drug sensitivity analyses were analyzed. External datasets were used to validate the predictive value of DRLs. qRT-PCR was also used to validate the differential expression of the target lncRNAs in tissue samples and cell lines. We established a prognostic signature for the DRLs (MKLN1-AS and TMCC1-AS1) in LIHC. The signature could divide the LIHC patients into low- and high-risk groups, with the high-risk subgroup associated with a worse prognosis. We observed discrepancies in tumor-infiltrating immune cells, immune function, function enrichment, and TIDE between two risk groups. LIHC patients in the high-risk group were more sensitive to several chemotherapeutic drugs. External datasets, clinical tissue, and cell lines confirmed the expression of MKLN1-AS and TMCC1-AS1 were upregulated in LIHC and associated with a worse prognosis. The novel signature based on the two DRLs provide new insight into LIHC prognostic prediction, TME, and potential therapeutic strategies.
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