Zhang Zichao, Wang Zhihui, Liu Yumeng, Zhao Li, Fu Weihua
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of General Surgery, First Hospital of Tsinghua University, Beijing 100016, China.
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of General Surgery, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
J Environ Pathol Toxicol Oncol. 2023;42(2):11-30. doi: 10.1615/JEnvironPatholToxicolOncol.2022043693.
Increasing evidence has shown that stromal interaction molecule 1 (STIM1), a key subunit of store-operated Ca2+ entry (SOCE), is closely associated with tumor growth, development, and metastasis. However, there is no report of a comprehensive assessment of STIM1 in pan-cancer. This study aimed to perform a general analysis of STIM1 in human tumors, including its molecular characteristics, functional mechanisms, clinical significance, and immune infiltrates correlation based on pan-cancer data from The Cancer Genome Atlas (TCGA). Gene expression analysis was investigated using TCGA RNA-seq data, the Tumor Immune Estimation Resource (TIMER). Phosphorylation analysis was undertaken using the Clinical Proteomic Tumor Analysis Consortium (CP-TAC) and the PhosphoNET database. Genetic alterations of STIM1 were analyzed using cBioPortal. Prognostic analysis was via the R package "survival" function and the Kaplan-Meier plotter. Functional enrichment analysis was via by the R package "cluster Profiler" function. The association between STIM1 and tumor-infiltrating immune cells and immune markers was by the R package "GSVA" function and TIMER. STIM1 was differentially expressed and associated with distinct clinical stages in multiple tumors. The phosphorylation of STIM1 at S673 is highly expressed in clear cell renal carcinoma and lung adenocarcinoma tumors compared to normal tissues. STIM1 genetic alterations correlate with poor prognosis in several tumors, including ovarian cancer and lung squamous cell carcinomas. High STIM1 expression is associated with good or poor prognosis across diverse tumors. Overall survival (OS) analysis indicated that STIM1 is a favorable prognostic factor for patients with BRCA, KIRC, LIHC, LUAD, OV, SARC, and UCEC, and is a risk prognostic factor for BLCA, KIRP, STAD, and UVM. There is a close correlation between STIM1 expression and immune cell infiltration, immune-regulated genes, chemokines, and immune checkpoints in a variety of tumors. STIM1 functions differently in diverse tumors, playing an oncogenic or antitumor role. Moreover, It may serve as a prognostic biomarker and an immunotherapy target across multiple tumors.
越来越多的证据表明，基质相互作用分子1（STIM1）作为储存性钙内流（SOCE）的关键亚基，与肿瘤的生长、发展和转移密切相关。然而，目前尚无关于泛癌中STIM1综合评估的报道。本研究旨在基于癌症基因组图谱（TCGA）的泛癌数据，对人类肿瘤中的STIM1进行全面分析，包括其分子特征、功能机制、临床意义以及与免疫浸润的相关性。使用TCGA RNA测序数据、肿瘤免疫评估资源（TIMER）进行基因表达分析。使用临床蛋白质组肿瘤分析联盟（CP-TAC）和PhosphoNET数据库进行磷酸化分析。使用cBioPortal分析STIM1的基因改变。通过R包“survival”函数和Kaplan-Meier绘图仪进行预后分析。通过R包“cluster Profiler”函数进行功能富集分析。通过R包“GSVA”函数和TIMER分析STIM1与肿瘤浸润免疫细胞和免疫标志物之间的关联。STIM1在多种肿瘤中差异表达，并与不同的临床分期相关。与正常组织相比，S673位点磷酸化的STIM1在透明细胞肾细胞癌和肺腺癌肿瘤中高表达。STIM1基因改变与包括卵巢癌和肺鳞状细胞癌在内的多种肿瘤的不良预后相关。在不同肿瘤中，高STIM1表达与良好或不良预后相关。总生存（OS）分析表明，STIM1是乳腺癌（BRCA）、肾透明细胞癌（KIRC）、肝癌（LIHC）、肺腺癌（LUAD）卵巢癌（OV）、肉瘤（SARC）和子宫内膜癌（UCEC）患者的有利预后因素，是膀胱癌（BLCA）、肾乳头状细胞癌（KIRP）、胃癌（STAD）和葡萄膜黑色素瘤（UVM）的风险预后因素。在多种肿瘤中，STIM1表达与免疫细胞浸润、免疫调节基因、趋化因子和免疫检查点之间存在密切相关性。STIM1在不同肿瘤中发挥不同作用，具有致癌或抗肿瘤作用。此外，它可能作为多种肿瘤的预后生物标志物和免疫治疗靶点。
