Aberrant methylation of the PTPRO gene in peripheral blood as a potential biomarker in esophageal squamous cell carcinoma patients

Abstract

Inactivation of protein tyrosine phosphatase receptor-type O (PTPRO), a new member of the PTP family, by hypermethylation has been described in several forms of cancers. We evaluated PTPRO hypermethylation as a potential epigenetic biomarker in esophageal squamous cell carcinoma (ESCC). PTPRO hypermethylation was observed in 27 (75%) of 36 primary tumors and correlated significantly with depth of invasion (T-stage, P = 0.013). Among matched peripheral blood samples from ESCC patients, 13 (36.1%) of 36 had detectable methylated PTPRO in plasma, and 15 (41.7%) of 36 had it in the buffy coat. No methylated PTPRO was observed in normal peripheral blood samples from 10 healthy individuals. In addition, demethylation by 5-aza-dC treatment led to gene reactivation in PTPRO-methylated and -silenced ESCC cell lines. This is the first report for detection of PTPRO as a non-invasive biomarker for solid tumors in peripheral blood. Our findings suggest that hypermethylated PTPRO occurs frequently in ESCC. Its detection in the peripheral blood of ESCC patients illustrates its potential clinical application as an epigenetic biomarker for noninvasive diagnosis and disease monitoring.

MethSurv: A Web Tool to Perform Multivariable Survival Analysis Using DNA Methylation Data

“…PTPRO promoter hyper methylation associated with a poorer survival rate for breast cancer The tumor suppressor properties of PTPRO gene have been evaluated across various cancer types such as esophageal carcinoma [40] and breast cancer [41]. A study by Li et al [42] included 98 primary breast tumor samples (not included in the TCGA database) from Shenzhen Maternal and Child Health Hospital showed that PTPRO promoter hyper methylation is associated with poorer overall survival (HR = 2.7; 95% CI: 1.1-6.2; p = 0.023).…”

The oncogenic roles of nuclear receptor coactivator 1 in human esophageal carcinoma

“…[29][30][31][32][33][34][35][36] The prognosis of ESCC remains to be poor with 5-year survival rate <20%. [37][38][39][40][41] In this study, we found that NCOA1 is highly enriched in human ESCC, and the levels of NCOA1 are clinically important in ESCC progression and patient prognosis. Functional studies demonstrated that NCOA1 is capable of promoting ESCC cell growth and progression.…”

“…Esophageal squamous cell carcinoma (ESCC) is the third most common malignancy of the digestive tract and the fifth leading cause of cancer‐related death worldwide . The prognosis of ESCC remains to be poor with 5‐year survival rate <20% . In this study, we found that NCOA1 is highly enriched in human ESCC, and the levels of NCOA1 are clinically important in ESCC progression and patient prognosis.…”

Survival and Inflammation Promotion Effect of PTPRO in Fulminant Hepatitis Is Associated with NF-κB Activation

“…For example, hepatocytes contain the full-length PTPRO protein, whereas it appears as a truncated form (PTPROt) in T cells, which are some of the main infiltrating inflammatory cells during FH. Most studies of PTPRO's role focused on cancer research; a common goal has been to define PTPRO as a tumor suppressor candidate (5)(6)(7)(8). Very recently, we (5) reported that PTPRO inhibits development of hepatocellular carcinoma by suppression of JAK2/STAT3 signaling; however, its role in liver inflammation is largely unknown.…”