全面的泛癌分析表明VSIR是一种潜在的免疫、诊断和预后生物标志物。
Comprehensive pan-cancer analysis reveals VSIR as a candidate immunologic, diagnostic, and prognostic biomarker.
作者信息
Pan Jun, Mahsud Ihsanullah, Ul Haq Moeen, Khan Salman, Alhomrani Majid, Alamri Abdulhakeem S, Alghamdi Saleh A, ALSuhaymi Naif, Baothman Bandar K, Almaghrabi Sarah, Ullah Sajid, Jamil Muhammad
机构信息
Department of Thoracic Surgery/Cardiovascular Surgery, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University Hangzhou 311200, Zhejiang, China.
Medical Department, Gomal Medical College/MTI D.I.Khan, Pakistan.
出版信息
Am J Transl Res. 2024 May 15;16(5):1630-1642. doi: 10.62347/JMBZ8836. eCollection 2024.
OBJECTIVES
Being a checkpoint, the expression level of V-set immunoregulatory receptor (VSIR) serves as an indicator of the extent of immunosuppression. Our objective was to undertake a pan-cancer analysis to examine the expression, genetic alterations, prognosis, and immunologic features associated with VSIR.
METHODS
The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), GEPIA2, UALCAN, OncoDB, Human Protein Atlas (HPA), STRING, DAVID, cell culture, clinical sample collection, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used.
RESULTS
This study comprehensively assessed VSIR across 33 cancers using TCGA and GTEx databases. Differential expression analysis revealed elevated VSIR in several cancers, notably in cholangiocarcinoma, esophageal carcinoma, kidney renal cell carcinoma, and liver hepatocellular carcinoma, while decreased expression was observed in various others. Prognostic analysis highlighted its significant association with reduced overall survival (OS) in ESCA and LIHC. Investigation into cancer stages demonstrated a correlation between VSIR expression and stage in ESCA and LIHC. Promoter methylation analysis indicated decreased VSIR methylation levels in tumors, implicating a role in oncogenesis. Furthermore, subcellular localization predictions, Tumor Mutational Burden (TMB), and Microsatellite Instability (MSI) correlations revealed intriguing insight into VSIR's function. Notably, a positive correlation was identified between VSIR expression and various immune cells in both cancers. Protein-protein interaction (PPI) network construction and gene enrichment analysis elucidated VSIR-associated dysregulated pathways, emphasizing its possible involvement in diverse pathways. Finally, experimental validation using LIHC clinical samples and cell lines confirmed elevated VSIR expression, supporting its oncogenic role.
CONCLUSION
Collectively, these findings present a comprehensive understanding of VSIR's diverse roles and potential clinical implications in ESCA and LIHC.
目的
作为一种检查点，V 集免疫调节受体（VSIR）的表达水平可作为免疫抑制程度的指标。我们的目的是进行一项泛癌分析，以研究与 VSIR 相关的表达、基因改变、预后和免疫特征。
方法
使用了癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）、GEPIA2、UALCAN、OncoDB、人类蛋白质图谱（HPA）、STRING、DAVID、细胞培养、临床样本收集以及逆转录定量聚合酶链反应（RT-qPCR）。
结果
本研究使用 TCGA 和 GTEx 数据库全面评估了 33 种癌症中的 VSIR。差异表达分析显示，VSIR 在几种癌症中表达升高，尤其是在胆管癌、食管癌、肾细胞癌和肝细胞癌中，而在其他多种癌症中表达降低。预后分析强调其与食管癌（ESCA）和肝细胞癌（LIHC）总体生存率（OS）降低显著相关。对癌症分期的研究表明，ESCA 和 LIHC 中 VSIR 表达与分期之间存在相关性。启动子甲基化分析表明肿瘤中 VSIR 甲基化水平降低，提示其在肿瘤发生中的作用。此外，亚细胞定位预测、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）相关性揭示了对 VSIR 功能的有趣见解。值得注意的是，在这两种癌症中均发现 VSIR 表达与多种免疫细胞呈正相关。蛋白质-蛋白质相互作用（PPI）网络构建和基因富集分析阐明了与 VSIR 相关的失调途径，强调其可能参与多种途径。最后，使用 LIHC 临床样本和细胞系进行的实验验证证实了 VSIR 表达升高，支持了其致癌作用。
结论
总体而言，这些发现全面了解了 VSIR 在 ESCA 和 LIHC 中的多种作用及潜在临床意义。
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