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全面分析 PTPN13 在乳腺癌中的表达及其临床意义。

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

机构信息

Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Shijiazhuang, China.

出版信息

Neoplasma. 2023 Apr;70(2):188-198. doi: 10.4149/neo_2023_221117N1110. Epub 2023 Feb 23.

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)的一个潜在生物标志物,但它在 BRCA 中的遗传变异和生物学意义尚不清楚。在此,我们全面研究了 PTPN13 表达/基因突变在 BRCA 中的临床意义。在我们的研究中,共纳入了 14 例接受新辅助治疗的三阴性乳腺癌(TNBC)患者,收集了手术后的 TNBC 组织进行下一代测序(NGS)分析(包括 PTPN13 在内的 422 个基因)。根据无病生存(DFS)时间,将 14 例 TNBC 患者分为 A 组(DFS 时间长)和 B 组(DFS 时间短)。NGS 数据显示,PTPN13 的总突变率为 28.57%,是第三大突变基因,且仅在 DFS 时间短的 B 组中出现 PTPN13 突变。此外,癌症基因组图谱(TCGA)数据库显示,PTPN13 在 BRCA 中的表达低于正常乳腺组织。然而,来自 Kaplan-Meier plotter 的数据表明,PTPN13 高表达与 BRCA 的良好预后相关。此外,基因集富集分析(GSEA)表明,PTPN13 可能参与了 BRCA 中的干扰素信号、JAK/STAT 信号、Wnt/β-catenin 信号、PTEN 通路和 MAPK6/MAPK4 信号。本研究提供了证据表明,PTPN13 可能是一种肿瘤抑制基因,也是 BRCA 的潜在分子靶点,PTPN13 的遗传突变和/或低表达预示着 BRCA 的预后不良。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。

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