Diagnosis and prognosis potential of four gene promoter hypermethylation in prostate cancer

Abstract

The current prostate special antigen (PSA) test causes the overtreatment of indolent prostate cancer (PCa). It also increases the risk of delayed treatment of aggressive PCa. DNA methylation aberrations are important events for gene expression dysregulation during tumorigenesis and have been suggested as novel candidate biomarkers for PCa. This may improve the diagnosis and prognosis of PCa. This study assessed the differential methylation and messenger RNA (mRNA) expression between normal and PCa samples. Correlation between promoter methylation and mRNA expression was estimated using Pearson's correlation coefficients. Moreover, the diagnostic potential of candidate methylation markers was estimated by the receiver operating characteristic (ROC) curve using continuous beta values. Survival and Cox analysis was performed to evaluate the prognostic potential of the candidate methylation markers. A total of 359 hypermethylated sites 3435 hypomethylation sites, 483 upregulated genes, and 1341 downregulated genes were identified from The Cancer Genome Atlas database. Furthermore, 17 hypermethylated sites (covering 13 genes), including known genes associated with hypermethylation in PCa (e.g., AOX1 and C1orf114), showed high discrimination between adjacent normal tissues and PCa samples with the area under the ROC curve from 0.88 to 0.94. Notably, ANXA2, FGFR2, HAAO, and KCNE3 were identified as valuable prognostic markers of PCa through the Kaplan–Meier analysis. Using gene methylation as a continuous variable, four promoter hypermethylation was significantly associated with disease‐free survival in univariate Cox regression and multivariate Cox regression. This study identified four novel diagnostic and prognostic markers for PCa. The markers provide important strategies for improving the timely diagnosis and prognosis of PCa.

ANXA2 is a potential biomarker for cancer prognosis and immune infiltration: A systematic pan-cancer analysis

“…ANXA2 showed a high diagnostic efficacy in 12 types of cancer, including CHOL, GBM, KICH, KIRP, LIHC, OV, PAAD, PRAD, READ, STAD, TGCT and THYM. Consistently with our findings, previous studies demonstrated a diagnostic value of ANXA2 in LIHC ( Zhang et al, 2012b ), PAAD ( Zhang et al, 2022 ) and PRAD ( Li et al, 2021 ). In the survival analysis, the expression of ANXA2 correlated with OS, PFI and DSS in several types of tumors.…”

Systematic Elucidation of the Aneuploidy Landscape and Identification of Aneuploidy Driver Genes in Prostate Cancer

“…It was also suggested that methylation of GSTM2 significantly correlated with the prognosis of PCa (Angulo et al, 2016). HAAO, which has been reported as the specific methylation biomarker for PCa, presented accurate discrimination between PCa and normal control samples and significantly prognostic implications (Li et al, 2021;Litovkin et al, 2014;Mahapatra et al, 2012;Li et al, 2021;Litovkin et al, 2014;Mahapatra et al, 2012). CYP27A1, which is a P450 enzyme catalyzing androgenanabolism, was suggested to be regulated by both genetic and epigenetic processes in PCa (Maksymchuk and Kashuba, 2020).…”

Somatic mutations in homologous recombination pathway predict favorable prognosis after immunotherapy across multiple cancer types

“…Moreover, HR mutations were also associated with several epigenetics and transcriptomics driven events, including SSX1, KCNE3, KLHDC7A, CDR2L methylations and F11, PSG4, AC129926.1 abnormal expression. Brie y, SSX1 is an epigenetic target that give rise to the disturbances of interacting multiprotein complexes such as the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex in synovial sarcomas [48]; the hypermethylation of KCNE3 promoter is reported to be a diagnostic and prognostic biomarker in prostate cancer [49]; CDR2 is the main antigen for the onconeural antibody Yo, which is strongly associated with ovarian cancer [50]. It is notable that the role of KLHDC7A, F11, PSG4, and AC129926.1 have not previously been reported in cancers, and thus requires further exploration.…”