@Article{or.2023.028051,
AUTHOR = {WEI BAO, QIANGUANG HAN, XIAO GUAN, ZIJIE WANG, MIN GU},
TITLE = {Solute carrier-related signature for assessing prognosis and immunity in patients with clear-cell renal cell carcinoma},
JOURNAL = {Oncology Research},
VOLUME = {31},
YEAR = {2023},
NUMBER = {2},
PAGES = {181--192},
URL = {http://www.techscience.com/or/v31n2/52295},
ISSN = {1555-3906},
ABSTRACT = {<b>Background:</b> Clear-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. <b>Methods:</b> We 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. <b>Results:</b> <i>SLC25A23</i>, <i>SLC25A42</i>, <i>SLC5A1</i>, <i>SLC3A1</i>, <i>SLC25A37</i>, <i>SLC5A6</i>, <i>SLCO5A1</i>, and <i>SCP2</i> 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 (<i>p</i> < 0.001). The risk score was an independent predictive indicator of ccRCC in the two cohorts according to univariate and multivariate Cox regression (<i>p</i> < 0.05). Analysis of the immune microenvironment showed that immune cell infiltration and immune checkpoint gene expression differed between the two groups (<i>p</i> < 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 (<i>p</i> < 0.001). Survival analysis and receiver operating characteristic curves were validated using the E-MTAB-1980 cohort. <b>Conclusions:</b> SLC-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.},
DOI = {10.32604/or.2023.028051}
}