Abstract
BackgroundProtein tyrosine phosphatase non-receptor type 12 (PTPN12), has been identified as a potent tumor suppressor in human cancers and a critical regulator of cell adhesion and migration. However, the PTPN12 expression and its prognostic significance in HCC have not been well elucidated.Methodology/Principal FindingsIn this study, tissue microarray-based immunohistochemistry (IHC) was investigated in an HCC cohort with adjacent liver tissues as controls. The resulting data were analyzed using receiver operating characteristic curves, Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression modeling. Our results showed that decreased expression of PTPN12 was more frequently observed in HCC tissues compared to the adjacent non-tumorous liver tissues. Further correlation analyses indicated that the decreased PTPN12 expression was closely correlated with tumor recurrence (P = 0.015). Univariate analysis showed a significant association between decreased expression of PTPN12 and adverse cancer-specific survival and recurrence-free survival (P<0.001). In different subsets of overall patients, PTPN12 expression was also a prognostic indicator in patients with stage I/II or stage III/IV (P<0.05). Importantly, multivariate analysis (P<0.05) identified PTPN12 expression in HCC as an independent prognostic factor.Conclusions/SignificanceOur findings provide a basis for the concept that PTPN12 protein expression is frequently decreased or lost in human HCC tissues and that decreased PTPN12 expression may represent an acquired recurrence phenotype of HCC and that PTPN12 expression may act as a biomarker of prognosis for patients with HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers worldwide
Cancers with scores above the obtained cutoff value were considered to have normal Protein tyrosine phosphatase non-receptor type 12 (PTPN12) expression, which led to the greatest number of cancers classified, based on the presence or absence of a clinical outcome
According to the Receiver operating characteristic (ROC) curve analysis, decreased expression of PTPN12 could be detected in 147/248 (59.3%) of HCCs and in 102/248 (41.1%) of adjacent liver tissues, respectively
Summary
Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers worldwide. The identification of novel genetic biomarkers is of important because this would allow early detection of HCC, provide new therapeutic targets for cancer treatments, and improve overall survival for HCC patients. Protein tyrosine phosphatases (PTPs) play a crucial role in cellular physiology, signal transduction and carcinogenesis [6,7]. There is an increasing body of evidence that decreased expression of PTPN12 occurs in various human malignancies, including breast cancer, colon cancer, ovarian cancer and esophageal squamous cell carcinoma [9,10,13,14]. Protein tyrosine phosphatase non-receptor type 12 (PTPN12), has been identified as a potent tumor suppressor in human cancers and a critical regulator of cell adhesion and migration. The PTPN12 expression and its prognostic significance in HCC have not been well elucidated
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