肿瘤细胞治疗研究
英文原题：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.
简言之，PVALB 是一种预后指标，其低表达通过影响 NK 细胞浸润促进 HCC 进展。
目的：肝细胞癌（HCC）是最常见的原发性肝癌，预后较差。肝脏复杂的免疫微环境与 HCC 发生有关。PVALB 是一种钙结合蛋白，在甲状腺癌和胶质瘤中被描述为肿瘤抑制基因，但其在 HCC 中的作用尚不明确。 材料与方法：从 TCGA 和 GSE54236 数据集获取数据。应用 MCP-counter、加权基因共表达网络分析（WGCNA）和 LASSO 模型筛选 PVALB。通过 UALCAN、MethSurv 等网站分析 PVALB 表达、甲基化和生存。使用 LinkedOmics 和 GSEA 开展功能分析，并通过 TIMER、TISIDB、Kaplan-Meier plotter 和 TIDE 数据库评估 PVALB 与肿瘤免疫微环境的关联、预测免疫治疗疗效。利用 TargetScan、DIANA、LncRNASNP2 数据库及相关实验构建 ceRNA 网络。最后通过 GeneMANIA、CTD 等分析 PVALB 分子对接和药物敏感性。 结果：PVALB 被确定为与 HCC 及 NK 细胞相关的基因。其在 HCC 组织中表达下调，与不良预后相关；PVALB 低甲基化也与其表达降低相关。值得注意的是，PVALB 与免疫密切相关，其表达降低可通过 Fas/FasL 通路削弱 NK 细胞抗癌作用，导致不良结局。lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB 轴可能调节 PVALB 表达。最后研究发现，免疫治疗可能是一种可行治疗选择。 结论：PVALB 是一种预后指标，其低表达可能通过影响 NK 细胞浸润促进 HCC 进展。
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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