Wang Xiaohui, Hussain Mumtaz, Ain Qurat Ul, Zaynab Madiha, Abdel-Maksoud Mostafa A, Almana Taghreed N, Almutair Saeedah, Alamri Abdulaziz, Saleh Ibrahim A, Zomot Naser, Al-Qahtani Wahidah H, Siddique Faisal, Hameed Yasir
Department of Dentistry, Henan Provincial Key Medicine Laboratory of Nursing, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China.
Department of Anatomy, Peoples University of Medical and Health Sciences, Nawabshah, Pakistan.
Discov Oncol. 2025 Aug 25;16(1):1611. doi: 10.1007/s12672-025-03384-4.
Cancer remains a leading cause of mortality worldwide, characterized by complex genetic and molecular alterations. The Protein Tyrosine Phosphatase Non-Receptor Type 6 (PTPN6), also known as SHP-1, plays a critical role in regulating immune responses and cellular signaling pathways, with emerging evidence suggesting its involvement in cancer progression. Previous studies have linked aberrant PTPN6 expression to tumorigenesis in specific cancers, such as lymphoma and leukemia, where it acts as a tumor suppressor. However, the comprehensive role of PTPN6 across pan-cancer, particularly its prognostic significance and molecular functions, has not been fully elucidated.
This study aimed to provide a pan-cancer analysis of PTPN6, utilizing data from multiple public databases with molecular in vitro experiments.
Our findings showed notable differences in PTPN6 expression among different cancer types. Prognostic analyses indicated that higher PTPN6 expression is associated with poorer overall survival in with notable upregulation in kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), and rectum adenocarcinoma (READ). Further, promoter methylation and mutation analyses highlighted alterations in PTPN6 expression across different cancer stages, with a particular reduction in methylation observed in tumor tissues. Functional assays in cell lines demonstrated that PTPN6 promotes cell proliferation, migration, and colony formation, supporting its role in cancer progression.
This comprehensive analysis emphasizes the potential of PTPN6 as both a prognostic biomarker and a therapeutic target in cancer. However, further research is required to fully elucidate its role in cancer progression and to assess its clinical applicability.
癌症仍然是全球主要的死亡原因，其特征是复杂的基因和分子改变。蛋白酪氨酸磷酸酶非受体6型（PTPN6），也称为SHP-1，在调节免疫反应和细胞信号通路中起关键作用，越来越多的证据表明它参与癌症进展。先前的研究已将异常的PTPN6表达与特定癌症（如淋巴瘤和白血病）的肿瘤发生联系起来，在这些癌症中它作为一种肿瘤抑制因子发挥作用。然而，PTPN6在泛癌中的全面作用，特别是其预后意义和分子功能，尚未完全阐明。
本研究旨在利用多个公共数据库的数据和分子体外实验，对PTPN6进行泛癌分析。
我们的研究结果显示不同癌症类型之间PTPN6表达存在显著差异。预后分析表明，PTPN6表达较高与总体生存率较差相关，在肾透明细胞癌（KIRC）、肝细胞癌（LIHC）和直肠腺癌（READ）中显著上调。此外，启动子甲基化和突变分析突出了不同癌症阶段PTPN6表达的改变，在肿瘤组织中观察到甲基化尤其减少。细胞系功能分析表明，PTPN6促进细胞增殖、迁移和集落形成，支持其在癌症进展中的作用。
这项综合分析强调了PTPN6作为癌症预后生物标志物和治疗靶点的潜力。然而，需要进一步研究以充分阐明其在癌症进展中的作用并评估其临床适用性。
