Introduction: The cell-surface ectonucleotidase CD39 is a key molecule of the immunosuppressive adenosine pathway within the tumor microenvironment. However, the relationship between CD39 and clear cell renal cell carcinoma (ccRCC) is rarely reported and still remains unclear.
Methods: CD39 expression was first analyzed using the Oncomine and the Tumor IMmune Estimation Resource (TIMER) databases, and then examined in ccRCC patients (n=367) who had undergone radical nephrectomy using immunohistochemistry (IHC) and real-time quantitative PCR analysis (qPCR). The prognosis value of CD39 in ccRCC was evaluated by Cox proportional hazards analysis. Functional and gene set enrichment analysis (GSEA) was performed using transcriptomic data of ccRCC from TCGA. Correlation analysis between CD39 and tumor-infiltrating lymphocytes (TILs) was performed using the TISIDB database. The impact of CD39 on immune checkpoint therapy (ICT) was evaluated by two public cohorts.
Results: CD39 mRNA and protein expression was upregulated in tumor tissues from ccRCC patients and aberrant expression of CD39 was associated with advanced tumor stage and poor prognosis in ccRCC patients. EMT, IL-2/STAT5, inflammatory response, interferon gamma and KRAS hallmark gene sets were identified as CD39-related signaling pathway. The expression level of CD39 was significantly and positively correlated with high abundance of the regulatory TILs including NK cells, macrophages, Th cells and Treg cells. CD39 was correlated with expression of several immune checkpoints and higher CD39 expression was associated with better OS of ccRCC patients who received ICT.
Conclusion: CD39 is a powerful prognostic marker of ccRCC patients. Increased tumor expression of CD39 mRNA is significantly correlated with infiltrating levels of TILs, and better efficacy of ICT to ccRCC. CD39 could be a novel therapeutic target for ccRCC.
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http://dx.doi.org/10.2147/OTT.S272553 | DOI Listing |
Transl Oncol
December 2024
Biotherapy Center, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China. Electronic address:
It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. In the present study, the expression of Response Gene to Complement 32 (RGC-32) was evaluated using immunohistochemistry.
View Article and Find Full Text PDFBiol Direct
December 2024
Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 Qingchun Road, Hangzhou, 310016, China.
Background: Precision oncology's implementation in clinical practice faces significant constraints due to the inadequacies in tools for detailed patient stratification and personalized treatment methodologies. Dysregulated tryptophan metabolism has emerged as a crucial factor in tumor progression, encompassing immune suppression, proliferation, metastasis, and metabolic reprogramming. However, its precise role in clear cell renal cell carcinoma (ccRCC) remains unclear, and predictive models or signatures based on tryptophan metabolism are conspicuously lacking.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Nephrology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Clear cell renal cell carcinoma (ccRCC) characterised by its diversity and a tendency to defy standard therapeutic approaches. Amidst the advent of immunotherapy, it has become imperative to pinpoint prognostic indicators of the tumour microenvironment (TME) influence the efficacy of treatments. Employing single-cell RNA sequencing (scRNA-seq), this research delved into the diverse landscape of ccRCC, uncovering its complex underpinnings and pinpointing molecular avenues for therapeutic intervention.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2024
Department of Equipment, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, Jiangsu, China.
Purpose: To create a nomogram for accurate prognosis of patients with clear cell renal cell carcinoma (ccRCC) based on computed tomography images.
Methods: Eight hundred twenty-two ccRCC patients with contrast-enhanced computed tomography images involved in this study were collected. A rectangular region of interest surrounding the tumor was used to extract quantitative radiomics and deep-learning features, which were filtered by Cox proportional hazard regression model and least absolute shrinkage and selection operator.
BJU Int
December 2024
Department of Urology, Zealand University Hospital, Roskilde, Denmark.
Objective: To identify predictors of metastases, estimate the proportion of metastatic clear cell renal cell carcinoma (ccRCC) cases according to these predictors, and subsequently create a risk table showing the absolute difference in metastasis proportion for each 10 mm increase in tumour size.
Patients And Methods: Patients diagnosed with histopathological confirmed ccRCC in 2010-2018 in Denmark identified in the nationwide Danish Multidisciplinary Renal Cancer Group (DaRenCa) Study-3. Association between diagnostic variables and metastases were assessed with logistic regression analyses.
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