Identification of fatty acid metabolism-based molecular subtypes and prognostic signature to predict immune landscape and guide clinical drug treatment in renal clear cell carcinoma.

ABSTRACT

Three subtypes of samples were generated based on genes involved in fatty acid metabolism in The Cancer Genome Atlas (TCGA)-RCC patients using a non-negative matrix factorization (NMF) algorithm. 32 co-expressed modules were identified using WCGNA. We constructed a four-gene signature in our training set using least absolute shrinkage selection operator regression analysis and verified it in our testing and overall sets. A relevant study analysis in clinical trials was conducted, which showed the model had good stability and potential application value for predicting outcomes. We analyzed the immune microenvironment using MCPcounter, CIBERSORT, quanTIseq, TIMER and ESTIMATE algorithms, and the result indicated risk was positively related to T cells, B-lineage, and fibroblasts and negatively correlated with monocytic lineage, myeloid dendritic cells, neutrophils, and endothelial cells, and CPT1B was positively related to T cells, CD8 + T cells, Cytotoxic lymphocytes and NK cells, and negatively correlated with myeloid dendritic cells, fibroblasts, endothelial cells. Tumor mutation burden was positively related to risk score and the expression of CPT1B using the R packages corrplot, circlize. Through the R package pRRophetic, drug sensitivity tests showed that the low-risk score group would benefit more from sunitinib and less from pazopanib, sorafenib, temsirolimus, gemcitabine and doxorubicin than the high-risk score group. We performed the relevant basic assay validation for CPT1B, and the proliferation ability of RCC cells was inhibited after the knockdown of protein expression of CPT1B. In conclusion, we established a four-gene model that can predict outcomes of RCC with potential applications in diagnosis and treatment.