Abstract
Mutations in the isocitrate dehydrogenase gene (IDH1) are involved in the progression of tumors. Although IDH1 has a role in various tumors, its clinical relevance and its expression in response to the immune response have not been investigated in prostate adenocarcinoma (PRAD). In the present study, we investigated the utility of IDH1 as a prognostic biomarker for PRAD by analyzing IDH1 mRNA expression and its association with patient survival and immune cell infiltration. IDH1 mRNA expression was significantly higher in PRAD tissue than in normal tissue, and Kaplan–Meier survival analysis showed that IDH1 expression was significantly associated with poor prognosis in PRAD patients. To elucidate the mechanisms involved, the correlation between IDH1 expression and the level of immune cell infiltration, in particular of immunosuppressive cells such as CD8+ T-cells, CD4+ T-cells, and macrophages, was further analyzed by single-cell RNA sequencing. We also screened a pharmacogenetic database for IDH1-specific drugs that inhibited high expression in PRAD. In the present study, we used a combination of databases to identify a significant correlation between IDH1 expression and cellular infiltration and to explain the mechanism by which IDH1 confers poor prognosis in PRAD, thus demonstrating the relevance of IDH1 expression as a prognostic biomarker with clinical utility in PRAD patients.
Highlights
Prostate adenocarcinoma (PRAD) is the most common cancer in men, and approximately 250,000 new cases of PRAD are diagnosed each year in America
We investigated whether genes with a >6.6% or higher mutation frequency in PRAD patients were altered in IDH family genes, or were altered in a more general way in other cancer types (Figure 2(a)). e TCGA and GEPIA2 data sets were used to compare IDH family gene expression and prognosis in patients with different reproductive tumor types
Characteristics, Mutations, and Copy Number Changes in PRAD. e TCGA database of prostate cancer patients (n 9329) was analyzed to identify changes in prostate cancer genes and to screen for potential biomarkers. e majority of prostate cancer malignancies in the database are attributed to prostate cancer (82.3%) and prostate adenocarcinoma (14.2%) (Figure 1(a)). e motif enrichment map uses red dots to mark the motifs on each chromosome
Summary
Prostate adenocarcinoma (PRAD) is the most common cancer in men, and approximately 250,000 new cases of PRAD are diagnosed each year in America. PRAD is characterized by a high mortality rate and was the second leading cause of cancer-related deaths among men in 2021 [1]. Determination of the genetic basis of PRAD has been challenging, and the identification of novel molecular biomarkers that could predict disease prognosis has been a research focus. E identification of such biomarkers will contribute to understanding of PRAD pathogenesis and provide precision management for patients with PRAD. IDH1 mutations are an important factor in early carcinogenesis. To understand the mechanisms of IDH1 and immune cell interactions in PRAD, in the present study, we analyzed a PRAD cohort from a multiomics database
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