Abstract：
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/β-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.
摘要：
蛋白酪氨酸磷酸酶非受体13（PTPN13）可能是乳腺癌（BRCA）的潜在生物标志物。但其在BRCA中的遗传变异和生物学意义仍不明确。在此，我们全面研究了BRCA中PTPN13表达/基因突变的临床意义。在我们的研究中,共纳入14例接受新辅助治疗的三阴性乳腺癌（TNBC）患者，收集术后TNBC组织进行下一代测序（NGS）分析（422个基因，包括PTPN13）。根据无病生存期（DFS）时间，将14例TNBC患者分为A组（长DFS）和B组（短DFS）。NGS数据显示，PTPN13的总体突变率为28.57％，是第三高的突变基因。PTPN13突变仅出现在具有短DFS的B组中。此外,癌症基因组图谱（TCGA）数据库表明，PTPN13在BRCA中的表达低于正常乳腺组织。然而,使用来自Kaplan-Meier绘图仪的数据，确定PTPN13高表达与BRCA的良好预后有关。此外，基因集富集分析(GSEA)显示PTPN13可能参与干扰素信号传导,JAK/STAT信号,Wnt/β-连环蛋白信号传导，BRCA中的PTEN通路和MAPK6/MAPK4信号传导。这项研究提供了证据，表明PTPN13可能是BRCA的抑癌基因和潜在的分子靶标，PTPN13基因突变和/或低表达预测BRCA预后不良。PTPN13在BRCA中的抗癌作用和分子机制可能与一些肿瘤相关的信号通路有关。
