Abstract
BackgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), which accounts for majority of RCC-related deaths. It is clearly essential to further identify more novel prognostic signatures and therapeutic targets.Material and MethodsWe identified differentially expressed genes (DEGs) between ccRCC and adjacent normal tissues in GEO database using a Robust Rank Aggregation (RRA) method. An mRNA signature (mRNASig) based on DEGs was developed using Cox and LASSO analysis in the TCGA database and validated in the ICGC database. Afterward, the influence of mRNASig mRNAs on the immune microenvironment in ccRCC was explored using comprehensive bioinformatics analysis.ResultsA total of 957 robust DEGs were identified using the RRA method. mRNASig comprised CEP55, IFI44, NCF4, and TCIRG1 and was developed and validated to identify high-risk patients who had poorer prognosis than low-risk patients. A nomogram was also constructed based on mRNASig, AJCC stage, and tumor grade. The mRNASig were closely related to a variety of tumor-infiltrating lymphocytes, especially including CD8+ T cells, activated CD4+ memory T cells, regulatory T cells, activated NK cells, and resting NK cells. The mRNASig were also correlated positively with the expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2.ConclusionWe developed and validated mRNASig to assist clinicians in making personalized treatment decisions. Furthermore, CEP55, IFI44, NCF4, and TCIRG1 may be novel potential targets for future treatment of ccRCC.
Highlights
The renal cell cancer (RCC) is a common malignant tumor of the urinary system with increasing incidence and accounts for 3% of all the new cancer cases (Siegel et al, 2020)
We found that CEP55, IFI44, NCF4, and T-cell immune regulator 1 (TCIRG1) were positively correlated with multiple tumorinfiltrating lymphocytes (TILs), especially including CD8+ T cells, activated CD4+ memory T cells, and Tregs
We found that mRNA signature (mRNASig) mRNAs were positively correlated with the expression of the above immune checkpoint inhibitors, showing that the poor prognosis of up-regulated mRNASig mRNAs may be related to the immunosuppressive microenvironment and mRNASig mRNAs may be novel potential targets for future treatment of Clear cell renal cell carcinoma (ccRCC)
Summary
The renal cell cancer (RCC) is a common malignant tumor of the urinary system with increasing incidence and accounts for 3% of all the new cancer cases (Siegel et al, 2020). According to the global cancer statistics of 2018, there were approximately 403,262 (2.2%) newly diagnosed cases and around 175,098 (1.8%) deaths due to RCC (Bray et al, 2018). A Novel ccRCC Signature (ccRCC) is the most common subtype of RCC and accounts for majority of RCC-related deaths (Hsieh et al, 2017). It is essential to identify more novel prognostic signatures and therapeutic targets. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), which accounts for majority of RCC-related deaths. It is clearly essential to further identify more novel prognostic signatures and therapeutic targets
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