Identification of PMF1 Methylation in Association with Bladder Cancer Progression

Abstract

PMF1 was identified to be epigenetically modified in bladder cancer. The association of PMF1 methylation with tumor progression and its diagnostic ability using urinary specimens support including PMF1 assessment for the clinical management of bladder cancer patients.

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric Cancers

“…Hypermethylation of the polyamine-modulated factor 1 (PMF1) gene has also been shown to be a strong indicator of tumor progression for bladder cancer patients (349 ). In addition, the loss of PMF1 protein expression has been reported to stratify bladder tumors histopathologically and predict clinical outcome (349,350 ).…”

“…In addition, the loss of PMF1 protein expression has been reported to stratify bladder tumors histopathologically and predict clinical outcome (349,350 ).…”

Comprehensive Genome Methylation Analysis in Bladder Cancer: Identification and Validation of Novel Methylated Genes and Application of These as Urinary Tumor Markers

“…In bladder cancer, methylation of single gene has been identified and a possible function as stage marker, or as a urinary marker, has been tested (13,19,(28)(29)(30)(31)(32)(33)(34)(35). However, few studies have used a more global array-based approach.…”

Hypermethylation in bladder cancer: biological pathways and translational applications

“…These include fine analyses of genomic regions being hypermethylated [56,128], and individual tumor suppresor candidates such as the Runt-related transcription factor 3 gene (RUNX3) [100,[129][130][131][132], myopodin, a cytoskeleton actin binding protein whose methylation was found useful to predict BCG response [133][134][135], the phosphatase and tensin homolog gene (PTEN) [58][59][60]130], the hypermethylated in cancer 1 gene (HIC1) [86,87,130], the Von Hippel-Lindau tumor suppresor gene (VHL) [58,59,68], the Wilms tumor 1 gene (WT1) [59,60], the deleted in bladder cancer,chromosomal region candidate 1 gene (DBCCR1) [128], the immunoglobulin superfamily member 4 gene (IGSF4) [58,59,91], or the deleted in breast cancer 1 gene (DBC1) [140]. Differentiation related genes have also been found methylated with high prevalence in bladder tumors such as the S-100 family of proteins [136], the Sry-related-hmg box 9 gene (SOX9) [47], the polyamine modulated factor 1 gene (PMF1) [137], the cancer antigen 1 gene (CAGE1) [130,138], the estrogen receptor gene (ESR1) [58][59][60]87], or the retinoic acid receptor gene (RARB) [58,59,105,139,…”

“…The initial studies have tried to evaluate whether urinary methylomes may serve for the diagnosis of the disease ( Table 1). The most studied genes reporting to play a potential diagnostic role with global accuracies over 65% in urinary specimens include CDKN2A [57, 58, 60, 67, 79, 83-85, 108, 115, 127], CCND2 [83], GSTP1 [58, 83-85, 108, 131], APC [57, 60, 83-85, 108, 142, 143], BRCA1 [58,131], RASFF1A [60, 71, 74, 79, 83-85, 105, 108, 115, 131, 142, 143], BCL2 [60,74,101,131,142], CDH1 [60,84,105,108,127], SFRP1 [57,115,124,127,140], SFRP2,4,5 [124,140], WIF1 [60,124,140,142], myopodin [134], PMF1 [137], and RARB [57,58,60,67,84,85,105,108,139,140], among others. These studies were initially performed by MS-PCR in qualitative or quantitative fashion modalities [67, 71, 74, 79, 83-85, 101, 105, 108, 110, 115, 119, 124, 126, 131, 139, 140, 142] and currently it is feasible by comprehensive multiplexed analyses such as by MS-MLPA …”