Comprehensive analysis of the PTPN13 expression and its clinical implication in breast cancer.

Protein tyrosine phosphatases non-receptor 13 (PTPN13) could be a potential biomarker in breast cancer (BRCA), but its genetic variation and biological significance in BRCA remain undefined. Hereon, we comprehensively investigated the clinical implication of PTPN13 expression/gene mutation in BRCA. In our study, a total of 14 cases of triple-negative breast cancers (TNBC) treated with neoadjuvant therapy were enrolled, and post-operation TNBC tissues were collected for next-generation sequencing (NGS) analysis (422 genes including PTPN13). According to the disease-free survival (DFS) time, 14 TNBC patients were divided into Group A (long-DFS) and Group B (short-DFS). The NGS data displayed that the overall mutation rate of PTPN13 was 28.57% as the third highest mutated gene, and PTPN13 mutations appeared only in Group B with short-DFS. In addition, The Cancer Genome Atlas (TCGA) database demonstrated that PTPN13 was lower expressed in BRCA than in normal breast tissues. However, PTPN13 high expression was identified to be related to a favorable prognosis in BRCA using data from the Kaplan-Meier plotter. Moreover, Gene Set Enrichment Analysis (GSEA) revealed that PTPN13 is potentially involved in interferon signaling, JAK/STAT signaling, Wnt/ß-catenin signaling, PTEN pathway, and MAPK6/MAPK4 signaling in BRCA. This study provided evidence that PTPN13 might be a tumor suppressor gene and a potential molecular target for BRCA, and genetic mutation and/or low expression of PTPN13 predicted an unfavorable prognosis in BRCA. The anticancer effect and molecular mechanism of PTPN13 in BRCA may be associated with some tumor-related signaling pathways.

[Potential effect of tumor necrosis factor-alpha and tumor necrosis factor receptor II gene polymorphisms on the pathogenesis of silicosis].

OBJECTIVE: To approach the role of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor receptor II (TNFR II) gene polymorphisms in genetic susceptibility to silicosis and their interaction with silica-dust exposure. METHODS: Two hundred and fifty-nine cases of silicosis and three hundred and forty-one silica-dust exposure workers (control) were selected, and the cases of silicosis were divided into three subgroups based on the various stages of I, II and III. Exposure history, pneumoconiosis history and past history of each subject were obtained by questionnaire. 3 ml peripheral venous blood was drawn from each subject. Using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques, TNF-alpha and TNFRII gene polymorphisms were analyzed. RESULTS: In both group matching and 1:1 paired matching, there was no significant difference between cases of silicosis and workers in control in distribution frequencies of G/A + A/A (TNF-alpha-308) and T/G + G/G (TNFRII 196) genotypes. The risk of silicosis in those with G/A + A/A genotype was 6.74-fold higher than G/G genotype (OR = 6.74, 95% CI: 1.01 approximately 44.99) in subjects whose exposure time was less than 15 years. CONCLUSION: TNF-alpha and TNFR II gene polymorphisms did not play an important role in susceptibility to silicosis of Han race. There was interaction between polymorphism of TNF-alpha gene promoter and exposure time in the occurrence of silicosis. The risk of silicosis in those with G/A + A/A genotype was significantly higher than G/G genotype in low accumulative exposure.