Transcriptome mapping of renal clear cell carcinoma revealed by machine learning algorithm based on enhanced computed tomography images

Abstract

Background: A growing number of studies have shown that inflammation-related components of the tumor microenvironment (TME) affect the clinical outcomes of cancer patients, and advances in radiomics may help predict survival and prognosis.Methods: We performed a systematic analysis of inflammation-related genes (IRGs) in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus and mapped their interaction network to assess the specific relationship between these differentially expressed inflammation-related genes (DEIRGs) and inflammation. The association between DEIRGs and prognosis was discussed and further validated using consensus cluster analysis. Next, we constructed IRGs-related risk score from the collected information and validated the prognostic value of the model using Kaplan-Meier survival analysis and receiver operating characteristic analysis. Computed tomographic images corresponding to the TCGA-ccRCC cohort were obtained from the Cancer Imaging Archive database for radiomics signature extraction. Results:We screened for prognostic IRGs and found that they were positively correlated with inflammatory cells in the tumor microenvironment associated with tumor progression and metastasis, such as activated CD8+ cells, myeloid-derived suppressor cells and neutrophils. The impact of IRGs on the prognosis of ccRCC patients was also verified. Using these differentially expressed genes, we successfully constructed a risk signature and validated its good prognosis assessment for patients. Furthermore, radiomics-based prognostic models performed better than those using risk signatures or clinical characteristics.Conclusions: IRG-related risk scores play an important role in assessing the prognosis and improving the management of patients with ccRCC. Through this feature, the infiltration of immune cells in the TME can be predicted. Furthermore, non-invasive radiomics signatures showed satisfactory performance in predicting ccRCC prognosis.

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma

“…Two main types of T cells, including CD 4 + T cells and CD 8 + T cells, have multifarious anti-tumor abilities, of which the former has the ability to harmonize the elaborate immune interactions and the latter can identify the superficial peptides on cells and assault antigen expression cells [ 40 , 41 ]. CD8 + T-cell infiltration prospectively predicts disease prognosis; unlike other tumors, elevated CD8 + T-cell level is associated with poor prognosis in ccRCC [ 42 ]. Meanwhile, another immune cell type of CD4 + T cells, as a cell subset, playing a momentous role in the TME and keeping strong immunosuppressive traits called Tregs (CD25 + cells).…”