Zhang Jinguo, Chen Jian, Shan Benjie, Lin Lin, Dong Jie, Sun Qingqing, Zhou Qiong, Han Xinghua
Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.
Front Med (Lausanne). 2021 Nov 16;8:752619. doi: 10.3389/fmed.2021.752619. eCollection 2021.
The soluble resistance-related calcium-binding protein (sorcin, SRI) serves as the calcium-binding protein for the regulation of calcium homeostasis and multidrug resistance. Although the mounting evidence suggests a crucial role of SRI in the chemotherapeutic resistance of certain types of tumors, insights into pan-cancer analysis of SRI are unavailable. Therefore, this study aimed to probe the multifaceted properties of SRI across the 33 cancer types. The SRI expression was analyzed The Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEX) database. The SRI genomic alterations and drug sensitivity analysis were performed based on the cBioPortal and the CellMiner database. Furthermore, the correlations among the SRI expression and survival outcomes, clinical features, stemness, tumor mutation burden (TMB), microsatellite instability (MSI), and immune cells infiltration were analyzed using TCGA data. The differential analysis showed that SRI was upregulated in 25 tumor types compared with the normal tissues. Aberrant expression of SRI was able to predict survival in different cancers. Further, the most frequent alteration of SRI genomic was amplification. Moreover, the aberrant SRI expression was related to stemness score, epithelial-mesenchymal-transition (EMT)-related genes, MSI, TMB, and tumor immune microenvironment in various types of cancer. TIMER database mining further found that the SRI expression was significantly correlated with the infiltration levels of various immune cells in certain types of cancer. Intriguingly, the SRI expression was negatively correlated with drug sensitivity of fluorouracil, paclitaxel, docetaxel, and isotretinoin. Our findings highlight the predictive value of SRI in cancer and provide insights for illustrating the role of SRI in tumorigenesis and drug resistance.
可溶性耐药相关钙结合蛋白(索辛,SRI)作为一种钙结合蛋白,用于调节钙稳态和多药耐药性。尽管越来越多的证据表明SRI在某些类型肿瘤的化疗耐药中起关键作用,但目前尚无关于SRI的泛癌分析的见解。因此,本研究旨在探究SRI在33种癌症类型中的多方面特性。利用癌症基因组图谱(TCGA)和基因型组织表达(GTEX)数据库分析了SRI的表达情况。基于cBioPortal和CellMiner数据库进行了SRI基因组改变和药物敏感性分析。此外,使用TCGA数据分析了SRI表达与生存结果、临床特征、干性、肿瘤突变负担(TMB)、微卫星不稳定性(MSI)和免疫细胞浸润之间的相关性。差异分析表明,与正常组织相比,SRI在25种肿瘤类型中上调。SRI的异常表达能够预测不同癌症的生存情况。此外,SRI基因组最常见的改变是扩增。此外,SRI的异常表达与多种癌症类型的干性评分、上皮-间质转化(EMT)相关基因、MSI、TMB和肿瘤免疫微环境有关。TIMER数据库挖掘进一步发现,SRI表达与某些癌症类型中各种免疫细胞的浸润水平显著相关。有趣的是,SRI表达与氟尿嘧啶、紫杉醇、多西他赛和异维甲酸的药物敏感性呈负相关。我们的研究结果突出了SRI在癌症中的预测价值,并为阐明SRI在肿瘤发生和耐药中的作用提供了见解。