Abstract
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 via 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.
Highlights
Recent statistics showed that cancer has become a worldwide public health issue with an estimated 1,898,160 new cancer cases and 608,570 cancer deaths in 2021 [1]
The results demonstrated that the SRI expression was significantly associated with increased microsatellite instability (MSI) in breast invasive carcinoma (BRCA), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), pancreatic adenocarcinoma (PAAD), thyroid carcinoma (THCA), and uterine corpus endometrial carcinoma (UCEC), while the SRI expression was negatively associated with MSI in colon adenocarcinoma (COAD), glioblastoma multiforme (GBM), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) (Figure 8A)
Regarding the SRI expression in normal tissues, our research revealed that the small intestine, brain tissues, and bone marrow had a high expression abundance of SRI, which was consistent with the reports of PaxDb database [18]
Summary
Recent statistics showed that cancer has become a worldwide public health issue with an estimated 1,898,160 new cancer cases and 608,570 cancer deaths in 2021 [1]. Great advances have been achieved in the diagnostics and treatment of cancer, in particular checkpoint blockade-based immunotherapy [2]. Pan-Cancer Analysis of Sorcin immunotherapy targets have attracted considerable attention among scientists. The SRI gene, which encodes the soluble resistance-related calcium-binding protein (sorcin), is located at chromosome 7q21.12 spanning about 21.9 kb of the human genome [3]. Sorcin serves as a calcium-binding protein that is a member of the penta-EF hand (PEF) family [4]. Sorcin holds a crucial role in the regulation of calcium homeostasis through diverse mechanisms. The role of SRI in cancer is receiving gradually more attention
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