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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

The Expression and Prognostic Value of Co-stimulatory Molecules in Clear Cell Renal Cell Carcinoma (CcRcc)

Author(s): Chengjiang Wu, Xiaojie Cai and Chunyan He*

Volume 27, Issue 2, 2024

Published on: 13 June, 2023

Page: [335 - 345] Pages: 11

DOI: 10.2174/1386207326666230511153724

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Abstract

Background: Renal cell carcinoma (RCC) was one of the most common malignant cancers in the urinary system. Clear cell carcinoma (ccRCC) is the most common pathological type, accounting for approximately 80% of RCC. The lack of accurate and effective prognosis prediction methods has been a weak link in ccRCC treatment. Co-stimulatory molecules played the main role in increasing anti-tumor immune response, which determined the prognosis of patients. Therefore, the main objective of the present study was to explore the prognostic value of co-stimulatory molecules genes in ccRCC patients.

Methods: The TCGA database was used to get gene expression and clinical characteristics of patients with ccRCC. A total of 60 co-stimulatory molecule genes were also obtained from TCGAccRCC, including 13 genes of the B7/ CD28 co-stimulatory molecules family and 47 genes of the TNF family. In the TCGA cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to generate a multigene signature. R and Perl programming languages were used for data processing and drawing. Real-time PCR was used to verify the expression of differentially expressed genes.

Results: The study's initial dataset included 539 ccRCC samples and 72 normal samples. The 13 samples have been eliminated. According to FDR<0.05, there were differences in the expression of 55 co-stimulatory molecule genes in ccRCC and normal tissues. LASSO Cox regression analysis results indicated that 13 risk genes were optimally used to construct a prognostic model of ccRCC. The patients were divided into a high-risk group and a low-risk group. Those in the high-risk group had significantly lower OS (Overall Survival rate) than patients in the low-risk group. Receiver operating characteristic (ROC) curve analysis confirmed the predictive value of the prognosis model of ccRCC (AUC>0.7). There are substantial differences in immune cell infiltration between high and low-risk groups. Functional analysis revealed that immune-related pathways were enriched, and immune status was different between the two risk groups. Real-time PCR results for genes were consistent with TCGA DEGs.

Conclusion: By stratifying patients with all independent risk factors, the prognostic score model developed in this study may improve the accuracy of prognosis prediction for patients with ccRCC.

Keywords: Clear cell renal cell carcinoma, immune infiltration, co-stimulatory molecules, prognostic score model, TCGA, ccRCC.

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