Comprehensive Analysis and Validation of Solute Carrier Family 25 (SLC25) and Its Correlation with Immune Infiltration in Pan-Cancer

Abstract

As the largest gene family functioning in protein transport among human solute carriers, the SLC25 family (mitochondrial carrier family) can participate in development of cancer. However, a comprehensive exploration for the exactly roles of SLC family remains lacking. In the present study, a total of 15 functional SLC25 family genes were retrieved from all current publications. And multidimensional analyses were systematically performed based on the transcriptome and genome data of SLC25 family from a variety of online databases for their expression, immune cell infiltration, and cancer prognosis. Validation by qPCR and immunohistochemistry were further conducted for the expression of partial SLC25 family members in some tumor tissue. We found that the SLC25 family had strong correlation with immune cells, such as macrophages M2, CD8+ T cell, CD4+ T cell memory activated, and memory resting. Among them, SLC25A6 was most correlated with Macrophage M1 in uveal melanoma ( r = − 0.68 , P = 1.9 e − 0.5 ). Expression of mRNA level showed that SLC25A4 was downregulated in stomach adenocarcinoma and colon adenocarcinoma. SLC25A7 was highly expressed in stomach adenocarcinoma and colon adenocarcinoma. SLC25A23 was decreased in colon adenocarcinoma. qPCR and immunohistochemistry validation results were consistent with our bioinformatics prediction. SLC25A8 was associated with the prognosis of cancer. All these findings suggested that the SLC25 family might affects the immune microenvironment of the cancer and then had the potential to be predictive biomarkers for early diagnosis and prognosis as well as novel targets for individualized treatment of cancer.

Unveiling the link between lactate metabolism and rheumatoid arthritis through integration of bioinformatics and machine learning

“…According to a recent study, tumor-associated macrophages (TAMs) may regulate the heme oxygenase (HO-1) expression level by controlling SLC25A4, promoting M2 macrophage polarization, and enhancing tumor metastasis. Meantime, particular flaws in SLC25A4 trigger the activation of hypoxia-inducible factor (HIF-1α) within inflammatory macrophages, consequently fostering heightened lactate dehydrogenase (LDH) expression levels and concurrent elevation in glycolysis 45 , 46 . Furthermore, studies have demonstrated the crucial role of regulatory T cells, natural killer cells, and dendritic cells in RA progression 47 , 48 .…”

Identification of Subtypes Associated with Pyroptosis and Immune Cell Death, Prediction using Prognostic Models, and Analysis of Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma

“…The physiological role of TPP1 is to recruit telomerase to chromosome ends and protect the ends from the ligations of unwanted material 32,33 . SLC25A4 is reportedly downregulated in gastric adenocarcinoma, colon adenocarcinoma, and renal cell carcinoma, compared with normal cells, and may, therefore, be used as a prognostic factor in renal cell carcinoma 34,35 . POMP promotes the assembly of 20S proteasome, leading to tumor suppressor gene p53 and retinoblastoma (Rb) through the ubiquitin-independent proteolysis, which promotes the occurrence of colorectal or rectal adenocarcinoma and multiple myeloma 36,37 .…”

Identification of genes showing altered DNA methylation and gene expression in the renal proximal tubular cells of rats treated with ochratoxin A for 13 weeks

“…Among other genes in the present OTA‐specific “mitochondrion” gene cluster, solute carrier (SLC)25A23, encoded by Slc25a23 , is a calcium‐dependent mitochondrial solute carrier involved in calcium uptake into mitochondria (Bassi et al, 2005). Multidimensional analyses systematically performed on the expression status (tissue mRNA, protein, and cell lines) of the SLC25 family from a pan‐cancer perspective based on a variety of online databases in human cancers revealed that SLC25 is one of the family members involved in the immune microenvironment of cancer (Liu et al, 2022). Among the SLC25 family of proteins, SLC25A7 is highly expressed in gastric adenocarcinoma and colon adenocarcinoma, whereas SLC25A23 is reported to be downregulated in colon adenocarcinoma (Liu et al, 2022).…”

“…Multidimensional analyses systematically performed on the expression status (tissue mRNA, protein, and cell lines) of the SLC25 family from a pan-cancer perspective based on a variety of online databases in human cancers revealed that SLC25 is one of the family members involved in the immune microenvironment of cancer (Liu et al, 2022). Among the SLC25 family of proteins, SLC25A7 is highly expressed in gastric adenocarcinoma and colon adenocarcinoma, whereas SLC25A23 is reported to be downregulated in colon adenocarcinoma (Liu et al, 2022). Furthermore, epigenetic downregulation of SLC25A23 has been observed in glioblastomas, and its low expression was associated with a poorer prognosis of glioblastomas (Sharma et al, 2017).…”