Dataset Information

The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma.

ABSTRACT:

Purpose

Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers with poor prognosis due to its rapid progression towards metastasis. Thus, finding clinically relevant biomarkers for early diagnosis, prognosis, and therapy prediction is essential. This study focused on the identification of SLC25A13 as a novel biomarker for SKCM and is aimed at investigating the biological functions of solute carrier family 25 member 13 (SLC25A13) in the development of SKCM.

Methods

GEPIA was used to analyze the diagnostic and prognostic values of SLC25A13 in SKCM using the TCGA dataset. PrognoScan was used to validate the prognostic value of SLC25A13 and its coexpressed genes in SKCM. TISIDB was established to reveal the relationship between the expression of SLC25A13 and immune infiltration in SKCM. The protein expression of SLC25A13 in SKCM was evaluated by the Human Protein Atlas. The signaling pathways and biological functions of SLC25A13 in SKCM were analyzed by LinkOmics. Metascape was applied to analyze the functional enrichment analysis of SLC25A13. Protein-protein interaction analysis of SLC25A13 was performed by GeneMANIA.

Results

The mRNA and protein levels of SLC25A13 in the SKCM were much higher than those in the normal tissue. Furthermore, the overexpression of SLC25A13 predicts worse outcomes of SKCM patients. Moreover, the SLC25A13 expression was negatively correlated with the immune infiltration level of SKCM. The overexpression of SLC25A13 coexpressed genes, such as ACLY and AFG3L2, and SCL25A13 interacting genes also predicted the unfavorable prognosis of SKCM patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of SLC25A13 coexpressed genes showed that these genes are enriched in ATPase activity, cell cycle, mTOR, and VEGFA-VEGFR2 signaling pathways, which were relevant to tumor development and angiogenesis. Gene set enrichment analysis (GSEA) demonstrated that the SLC25A13 expression was related to infiltrating immune cells in SKCM.

Conclusion

Our findings revealed that SLC25A13 might be a potential prognostic and therapeutic biomarker for SKCM.

SUBMITTER: Lv Y

PROVIDER: S-EPMC9124094 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma.

Lv Yue Y Yuan Chun-Hui CH Han Lu-Yao LY Huang Gao-Ru GR Ju Ling-Ce LC Chen Ling-Hui LH Han Hai-Ying HY Zhang Chong C Zeng Ling-Hui LH

Disease markers 20220514

<h4>Purpose</h4>Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers with poor prognosis due to its rapid progression towards metastasis. Thus, finding clinically relevant biomarkers for early diagnosis, prognosis, and therapy prediction is essential. This study focused on the identification of SLC25A13 as a novel biomarker for SKCM and is aimed at investigating the biological functions of solute carrier family 25 member 13 (SLC25A13) in the development of SKCM.<h4> ...[more]

PMID: 35607442

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Project description:BackgroundDNA damage repair plays an important role in the onset and progression of cancers and its resistance to treatment therapy. This study aims to assess the prognostic potential of DNA damage repair markers in skin cutaneous melanoma (SKCM).MethodIn this study, we have analyzed the gene expression profiles being downloaded from TCGA, GTEx, and GEO databases. We sequentially used univariate and LASSO Cox regression analyses to screen DNA repair genes associated with prognosis. Then, we have conducted a multivariate regression analysis to construct the prognostic profile of DNA repair-related genes (DRRGs). The risk coefficient is used to calculate the risk scores and divide the patients into two cohorts. Additionally, we validated our prognosis model on an external cohort as well as evaluated the link between immune response and the DRRGs prognostic profiles. The risk signature is compared to immune cell infiltration, chemotherapy, and immune checkpoint inhibitors (ICIs) treatment.ResultsAn analysis using LASSO-Cox stepwise regression established a prognostic signature consisting of twelve DRRGs with strong predictive ability. Disease-specific survival (DSS) is found to be lower among high-risk patients group as compared to low-risk patients. The signature may be employed as an independent prognostic predictor after controlling for clinicopathological factors, as demonstrated by validation on one external GSE65904 cohort. A strong correlation is also found between the risk score and the immune microenvironment, along with the infiltrating immune cells, and ICIs key molecules. The gene enrichment analysis results indicate a wide range of biological activities and pathways to be exhibited by high-risk groups. Furthermore, Cisplatin exhibited a considerable response sensitivity in low-risk groups as opposed to the high-risk incidents, while docetaxel exhibited a considerable response sensitivity in high-risk groups.ConclusionsOur findings provide a thorough investigation of DRRGs to develop an DSS-related prognostic indicator which may be useful in forecasting SKCM progression and enabling more enhanced clinical benefits from immunotherapy.

Project description:BackgroundIGF2BP3 expression is associated with poor prognosis in cancers of multiple tissue origins. However, the precise mechanism of its co-carcinogenic action in bladder cancer is unknown.MethodsWe aimed to demonstrate the relationship between IGF2BP3 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. We next validated IGF2BP3 expression in the Gene Expression Omnibus (GEO) database (GSE3167). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic values of IGF2BP3. Cox and logistic regression were used to explore the factors affecting the prognosis. Protein-protein interactions (PPIs) network was constructed by STRING. Enrichment analyses were performed to infer involved pathways and functional categories of IGF2BP3 using the cluster Profiler package. We applied single-sample gene set enrichment analysis (ssGSEA) algorithm and TIMER database to evaluate the expression level of immune genes.ResultsPan-cancer analyses reveal that IGF2BP3 was higher in most cancer types, including bladder cancer, and the same results were found in GSE3167. The area under the ROC curve of IGF2BP3 was 0.736, which indicated that IGF2BP3 may be a potential diagnostic biomarker. High IGF2BP3 expression was associated with poorer overall survival (OS) (P = 0.015). For validation, we collected 95 bladder cancer samples and found that IGF2BP3 expression was higher in bladder cancer tissues than that in non-tumor bladder tissues by immunohistochemistry staining. We found a positive correlation between the expression level of IGF2BP3 and the clinical stage of bladder cancer. Immunocyte infiltration analysis showed that high IGF2BP3 expression was correlated with regulating the infiltration level of immune cell, including neutrophil cells and macrophages. IGF2BP3 promotes migration and invasion of bladder cancer cells, while IGF2BP3 inhibition had the opposite effects. Higher IGF2BP3 expression was closely associated with advanced TNM stage.ConclusionIGF2BP3 overexpression was related to disease progression and poor prognosis, as well as infiltration of immune cells in bladder cancer. IGF2BP3 can be a promising independent prognostic biomarker and potential treatment target for bladder cancer.

Project description:Stress-associated endoplasmic reticulum protein 1 (SERP1) is a gene induced by endoplasmic reticulum (ER) stress and a major contributor to multiple tumor types. Skin cutaneous melanoma (SKCM) is a highly aggressive and fatal cancer with poor treatment outcomes after progression. In this study, we evaluated SERP1's role in tumorigenesis, prognosis, and immune infiltration in SKCM. Patients with SKCM had low SERP1 expression. We identified differentially expressed genes between high- and low-SERP1 expression groups and conducted functional, pathway, and gene enrichment analyses. Protein-protein (PPI) and gene-gene interaction (GGI) networks were constructed via STRING and GeneMANIA, respectively. SERP1 mutation information was obtained through cBioPortal; location in the skin was identified through the Human Protein Atlas. Kaplan-Meier analysis revealed an association between low SERP1 expression and overall survival (OS), disease-specific survival (DSS), progress-free interval (PFI) rates, and worse prognosis in patients with multiple clinicopathological features. Cox regression analysis and nomograms further presented SERP1 level as an independent prognostic factor for patients with SKCM. Furthermore, there were significant correlations between SERP1 expression and immune infiltrates; thus, low SERP1 expression is associated with immune cell infiltration and can be considered a poor prognostic biomarker in patients with SKCM. Stress-associated endoplasmic reticulum protein 1 (SERP1) is a gene induced by endoplasmic reticulum (ER) stress and a major contributor to multiple tumor types. Skin cutaneous melanoma (SKCM) is a highly aggressive and fatal cancer with poor treatment outcomes after progression. In this study, we evaluated SERP1's role in tumorigenesis, prognosis, and immune infiltration in SKCM. Patients with SKCM had low SERP1 expression. We identified differentially expressed genes between high- and low-SERP1 expression groups and conducted functional, pathway, and gene enrichment analyses. Protein-protein (PPI) and gene-gene interaction (GGI) networks were constructed via STRING and GeneMANIA, respectively. SERP1 mutation information was obtained through cBioPortal; location in the skin were identified through the Human Protein Atlas. Kaplan-Meier analysis revealed an association between low SERP1 expression and overall survival (OS), disease-specific survival (DSS), progress-free interval (PFI) rates, and worse prognosis in patients with multiple clinicopathological features. Cox regression analysis and nomograms further presented SERP1 level as an independent prognostic factor for patients with SKCM. Furthermore, there were significant correlations between SERP1 expression and immune infiltrates; thus, low SERP1 expression is associated with immune cell infiltration and can be considered a poor prognostic biomarker in patients with SKCM.

Project description:Objectives: The novel long non-coding RNA (lncRNA) LINC01094 is often upregulated in renal cell carcinoma and glioma; however, its role in gastric cancer remains unclear. Here, we aim to demonstrate the relationship between LINC01094 and gastric cancer. Method: The gene expression (RNASeq) data of 375 patients with localized, locally advanced, and metastatic gastric cancer were extracted from The Cancer Genome Atlas. The Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between the clinicopathological characteristics and LINC01094 expression. Cox regression analysis and the Kaplan-Meier method were used to assess prognostic factors of gastric cancer. A nomogram based on Cox multivariate analysis was used to predict the impact of LINC01094 on gastric cancer prognosis. Gene set enrichment analysis (GSEA) was used to identify key LINC01094-associated signaling pathways. Fluorescence in situ hybridization (FISH) was performed to detect the location of LINC01094 in the tissue, and a competing endogenous (ce)RNA network was constructed to identify LINC01094-related genes. Spearman's rank correlation was used to elucidate the association between LINC01094 expression level and immune cell infiltration level. Result: LINC01094 expression was upregulated in gastric cancer tissues and strongly associated with overall survival using univariate Cox regression (hazard ratio [HR] = 1.476, 95% CI = 1.060-2.054, P = .021) and multivariate Cox regression analysis (HR = 1.535, 95% CI = 1.021-2.308, P = .039). The area under the receiver operating characteristic curve of LINC01094 was 0.910. GSEA showed a strong relationship between LINC01094 and the epithelial-mesenchymal transition pathway. RNA-FISH demonstrated that LINC01094 localized in the cytoplasm. It was closely related to the epithelial-mesenchymal transition (EMT) marker SNAI2, according to ceRNA (R = 0.61, P < .001), and macrophage-related gene FCGR2A. Macrophages were also significantly positively correlated with LINC01094 expression (R = 0.747, P < .001). Conclusion: High LINC01094 expression predicts poor prognosis in gastric cancer and is correlated with the epithelial-mesenchymal transition pathway and macrophage infiltration.

Dataset Information

The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma.

Purpose

Methods

Results

Conclusion

Publications

The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma.

Similar Datasets

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