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. 2016 Sep 27;7(39):64043-64052.
doi: 10.18632/oncotarget.11581.

Methylation and expression of PTPN22 in esophageal squamous cell carcinoma

Jiaying Deng  1   2 , Junhua Zhang  1   2 , Chunyu Wang  1   2 , Qing Wei  3 , Daizhan Zhou  4 , Kuaile Zhao  1   2
Affiliations

Methylation and expression of PTPN22 in esophageal squamous cell carcinoma

Jiaying Deng et al. Oncotarget. .

Abstract

Esophageal squamous cell carcinoma (ESCC) is a fatal disease contributed by both genetic and epigenetic factors. The epigenetic alteration of protein tyrosine phosphatase non-receptor type 22 (PTPN22) and its clinical significance in ESCC were still not yet clarified. A quantitative methylation study of PTPN22 and its expression were conducted in 121 and 31 paired tumor and adjacent normal tissue (ANT), respectively. Moreover, the association between PTPN22 methylation and clinicopathological parameters was evaluated. We found that the methylation level of PTPN22 was significantly elevated in tumor tissues (66.3%) relative to ANT (62.1%) (p=0.005). The methylation level of non-smoking ANT (59.1%) was significant lower than smoking ESCC tissue (65.8%) (p=0.03); similarly, the methylation levels in ANT with no lymph node invasion (57.6%) were significant lower than tumor tissues with lymph node invasion (67.5%) (p=0.001). PTPN22 expression in ESCC was lower than normal tissues, however the difference was not statistically significant (p=0.55). Lower expression was more frequently occurred in N1-3 and III stage patients, while higher expression was more likely to occur in N0 and I-II stage patients. Lower expression of PTPN22 was associated with poor overall survival (p=0.04). Taken together, PTPN22 was hypermethylationed in ESCC. Hypermethylation was associated with lymph node invasion. The PTPN22 expression may act as a prognostic biomarker to identify patients at risk of high grade.

Keywords: ESCC; PTPN22; expression; methylation; prognosis.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interests.

Figures

Figure 1
Figure 1. Schematic diagram of the CpG sites in the selected region
The CpG sites are depicted by lollipop markers. The binding sites for the forward and reverse primers are depicted as arrows below the diagram.
Figure 2
Figure 2
A. The mean methylation level for each CpG site in PTPN22. ***represents p<0.001, **represents p<0.01, and *represents p<0.05; B. The mRNA expression level of PTPN22. *represents p<0.05.
Figure 3
Figure 3
A. Correlation of PTPN22 expression and lymph node invasion; B. Correlation of PTPN22 expression and TNM stage.
Figure 4
Figure 4. Kaplan–Meier estimates of overall survival for ESCC patients according to different PTPN22 expression levels
See this image and copyright information in PMC

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