PVALB被确定为与免疫密切相关的HCC独立预后因子,其缺失会通过调节NK细胞浸润加速肿瘤进展。

IF 4.2 3区 医学 Q2 ONCOLOGY
Journal of Hepatocellular Carcinoma Pub Date : 2024-05-08 eCollection Date: 2024-01-01 DOI:10.2147/JHC.S450479
Yiyang Gong, Minqin Zhou, Yanting Zhu, Jingying Pan, Xuanrui Zhou, Yike Jiang, Hong Zeng, Hao Zheng, Xitong Geng, Da Huang
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引用次数: 0

摘要

目的:肝细胞癌是最常见的原发性肝癌,预后不良。肝脏复杂的免疫微环境与 HCC 的发展有关。PVALB是一种钙结合蛋白,已被描述为甲状腺癌和胶质瘤的抑癌基因。然而,PVALB 在 HCC 中的作用尚不清楚:我们从 TCGA 和 GSE54236 数据集中获取数据。应用 MCP-counter、WGCNA 和 LASSO 模型识别 PVALB。通过 UALCAN、MethSurv 和其他网站,我们探究了 PVALB 的表达、甲基化和存活情况。采用LinkedOmics和GSEA进行功能分析,利用TIMER、TISIDB、Kaplan-Meier plotter和TIDE数据库评估PVALB与肿瘤免疫微环境的相关性,预测免疫治疗的疗效。利用TargetScan、DIANA、LncRNASNP2数据库和相关实验构建了ceRNA网络。最后,通过GeneMANIA、CTD等对PVALB的分子对接和药物敏感性进行了表征:结果:PVALB被认为是与HCC和NK细胞相关的基因。结果:PVALB 被认为是与 HCC 和 NK 细胞相关的基因,它在 HCC 组织中的表达下调,导致不良预后。此外,PVALB的低甲基化与其表达减少有关。值得注意的是,PVALB与免疫密切相关,它的表达减少会削弱NK细胞通过Fas/FasL途径的抗癌作用,从而导致不良预后。lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB轴可能调控PVALB的表达。最后,我们发现免疫疗法可能是一种可行的治疗方案:总而言之,PVALB是一个预后指标,其低表达通过影响NK细胞浸润而促进HCC的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PVALB Was Identified as an Independent Prognostic Factor for HCC Closely Related to Immunity, and Its Absence Accelerates Tumor Progression by Regulating NK Cell Infiltration.

Purpose: Hepatocellular carcinoma is the most common primary liver cancer, with poor prognosis. Complex immune microenvironment of the liver is linked to the development of HCC. PVALB is a calcium-binding protein which has been described as a cancer suppressor gene in thyroid cancer and glioma. Nevertheless, the role of PVALB in HCC is unknown.

Materials and methods: We obtained data from TCGA and GSE54236 datasets. MCP-counter, WGCNA and LASSO model were applied to identify PVALB. With UALCAN, MethSurv, and other websites, we probed the expression, methylation and survival of PVALB. LinkedOmics and GSEA were adopted for functional analysis, while TIMER, TISIDB, Kaplan-Meier plotter, TIDE databases were utilized to evaluate the relevance of PVALB to the tumor immune microenvironment and predict immunotherapy efficacy. TargetScan, DIANA, LncRNASNP2 databases and relevant experiments were employed to construct ceRNA network. Finally, molecular docking and drug sensitivity of PVALB were characterized by GeneMANIA, CTD, and so on.

Results: PVALB was recognized as a gene associated with HCC and NK cell. Its expression was down-regulated in HCC tissue, which lead to adverse prognosis. Besides, the hypomethylation of PVALB was related to its reduced expression. Notably, PVALB was tightly linked to immune, and its reduced expression attenuated the anticancer effect of NK cells via the Fas/FasL pathway, leading to a adverse outcome. The lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB axis may regulate the PVALB expression. Finally, we found immunotherapy might be a viable treatment option.

Conclusion: In a word, PVALB is a prognostic indicator, whose low expression facilitates HCC progression by impacting NK cell infiltration.

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来源期刊
CiteScore
0.50
自引率
2.40%
发文量
108
审稿时长
16 weeks
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