Dataset Information

High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma.

ABSTRACT: Solute Carrier Family 1, member 5 (SLC1A5), also named as ASCT2, a major glutamine transporter, is highly expressed in various malignancies and plays a critical role in the transformation, growth and survival of cancer cells. The aim of this study was to assess the clinical significance of SLC1A5 in patients with clear-cell renal cell carcinoma (ccRCC). SLC1A5 expression was evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier method was conducted to compare survival curves. Univariate and multivariate Cox regression models were applied to assess the impact of prognostic factors on overall survival (OS). A nomogram was then constructed on the basis of the independent prognosticators identified on multivariate analysis. The predictive ability of the models was compared using Receiver operating characteristic (ROC) analysis. Our data indicated that high expression of SLC1A5 was significantly associated with advanced TNM stage, higher Fuhrman grade and shorter OS in ccRCC patients. Multivariate analysis confirmed that SLC1A5 was an independent prognosticator for OS. A nomogram integrating SLC1A5 and other independent prognosticators was constructed, which showed a better prognostic value for OS than TNM staging system. In conclusion, high SLC1A5 expression is an independent predictor of adverse clinical outcome in ccRCC patients after surgery.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4657035 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma.

Liu Yidong Y Yang Liu L An Huimin H Chang Yuan Y Zhang Weijuan W Zhu Yu Y Xu Le L Xu Jiejie J

Scientific reports 20151124

Solute Carrier Family 1, member 5 (SLC1A5), also named as ASCT2, a major glutamine transporter, is highly expressed in various malignancies and plays a critical role in the transformation, growth and survival of cancer cells. The aim of this study was to assess the clinical significance of SLC1A5 in patients with clear-cell renal cell carcinoma (ccRCC). SLC1A5 expression was evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier method was conducted to compare survival curves. Uni ...[more]

PMID: 26599282

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Project description:BackgroundClear-cell renal cell carcinoma (ccRCC) is the most common malignant kidney cancer. However, the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.MethodsWe used The Cancer Genome Atlas to obtain ccRCC transcriptome data and clinical information. The E-MTAB-1980 cohort was used for external validation. The GENECARDS database contains the first 100 solute carrier (SLC)-related genes. The predictive value of SLC-related genes for ccRCC prognosis and treatment was assessed using univariate Cox regression analysis. An SLC-related predictive signature was developed through Lasso regression analysis and used to determine the risk profiles of patients with ccRCC. Patients in each cohort were separated into high- and low-risk groups based on their risk scores. The clinical importance of the signature was assessed through survival, immune microenvironment, drug sensitivity, and nomogram analyses using R software.ResultsSLC25A23, SLC25A42, SLC5A1, SLC3A1, SLC25A37, SLC5A6, SLCO5A1, and SCP2 comprised the signatures of the eight SLC-related genes. Patients with ccRCC were separated into high- and low-risk groups based on the risk value in the training and validation cohorts; the high-risk group had a significantly worse prognosis (p < 0.001). The risk score was an independent predictive indicator of ccRCC in the two cohorts according to univariate and multivariate Cox regression (p < 0.05). Analysis of the immune microenvironment showed that immune cell infiltration and immune checkpoint gene expression differed between the two groups (p < 0.05). Drug sensitivity analysis showed that compared to the low-risk group, the high-risk group was more sensitive to sunitinib, nilotinib, JNK-inhibitor-VIII, dasatinib, bosutinib, and bortezomib (p < 0.001). Survival analysis and receiver operating characteristic curves were validated using the E-MTAB-1980 cohort.ConclusionsSLC-related genes have predictive relevance in ccRCC and play roles in the immunological milieu. Our results provide insight into metabolic reprogramming in ccRCC and identify promising treatment targets for ccRCC.

Project description:Aim: To identify potential key candidate genes, whose expression and clinical significance was further assessed in colorectal cancer (CRC). Methods: Three original microarray datasets (GSE41328, GSE22598, and GSE23878) from NCBI-GEO were used to analyze differentially expressed genes (DEGs) in CRC. Online database analyses through Oncomine and GEIPA were performed to evaluate SLC4A4 expression and explore the prognostic merit of SLC4A4 expression, which was further confirmed by analyses from QPCR based cDNA array and IHC based tissue microarray (TMA). STRING website was used to explore the interaction between SLC4A4 with other DEGs based on the protein-protein interaction (PPI) networks. Results: Analysis of three original microarray datasets from GEO identified 82 shared, differentially expressed genes (28 upregulated and 54 down-regulated) in CRC tissues. Online analyses from Oncomine and GEIPA revealed lower SLC4A4 mRNA expression in CRC tissues compared to adjacent normal tissues, which were further confirmed by QPCR based cDNA array and IHC based TMA analyses on both mRNA and protein levels. Survival analyses through GEIPA and from TMA demonstrated that low SLC4A4 expression is correlated with worse overall survival among patients with CRC. Survival analysis from Kaplan-meier plotter demonstrated that low SLC4A4 expression is significantly associated with poor progression (including relapse-free survival, overall survival, distant metastasis-free survival, post-progression survival) of patients with breast cancer, lung cancer, gastric cancer, and ovarian cancer. PPI analysis found that SLC4A4 is highly correlated with various genes, including SLC9A3, SLC26A6, ENSG00000214921, SLC26A4, SLC9A3R1, and SLC9A1. Conclusion: The mRNA and protein levels of SLC4A4 were decreased in CRC tissues, and low expression of SLC4A4 significantly correlated with shorter survival of CRC patients and poorer progression of patients with breast cancer, lung cancer, gastric cancer and ovarian cancer, suggesting potential role of SLC4A4 on tumor suppression and prognostic prediction in multiple malignancies including CRC.

Dataset Information

High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma.

Publications

High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma.

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