Metabolic Understanding of the Genetic Dysregulation in the Tumor Microenvironment of Kidney Renal Clear Cell Carcinoma

Abstract

The metabolic dysregulation is a hallmark of cancers including KIRC, specifically caused by alterations in metabolic genes. Currently, a lack of consensus exists between metabolic signatures in the tumor microenvironment. Here, in this study, we observed the significant correlations of differentially expressed metabolic genes (DEmGs) between KIRC and the related normal samples. Briefly, we collected sets of metabolic genes through RNA-seq data of KIRC and normal tissues from TCGA, followed by the identification of KIRC-related DEmGs. Next, patients were classified into three clusters, and using WGCNA, we identified metabolic genes involved in the survival among different clusters. Furthermore, we investigated survival and clinical parameters along with immune infiltration in the clusters. At the same time, we constructed and validated a prediction model based on these DEmGs. These analyses revealed that the patients having high expression of DEmGs showed poor survival, while infiltration of less-immune cells was associated with the metastasis of KIRC. In the end, we identified NUDT1 as a hub gene as it showed significantly high expression in KIRC samples as well as associated with the survival and prognosis of the patients. Further analysis revealed the oncogenic role of NUDT1 in 786-O and ACHN cells. Thus, we conclude that NUDT1 could be a potential diagnostic and prognostic marker for KIRC.

A Novel 7-Methylguanosine (m7G)-Related Gene Signature for Overall Survival Prediction in Patient with Clear Cell Renal Cell Carcinoma

“…Up to now, the association between the NUDTfamily and tumorigenesis has been unclear, and studies about their role in ccRCC are rare [41][42][43]. Previous studies indicated that NUDT1 might provide diagnostic and prognostic value for KIRC [44]. A study revealed that NUDT1 is activated by HIF2αtranscription, thereby inhibiting oxidative stress and promoting the progression of ccRCC [45].…”

Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma

“…Kidney clear cell carcinoma (ccRCC) represents approximately 3% of all human malignancies and is the predominant tumor affecting the adult kidney, encompassing the majority of renal tumor cases (1). Recent studies have revealed the concerning fact that the incidence of Clear cell renal carcinoma (ccRCC) increases progressively with age, is associated with a number of lifestyle and genetic factors, and is now the 16th most important contributor to cancer-related mortality worldwide (2,3). Regrettably, the overall survival (OS) and recurrence-free survival rates associated with ccRCC remain suboptimal, necessitating the identification of novel therapeutic targets and prognostic biomarkers.…”