PTPN1 是一种与癌症免疫和药物敏感性相关的预后生物标志物:从泛癌分析到乳腺癌验证。
PTPN1 is a prognostic biomarker related to cancer immunity and drug sensitivity: from pan-cancer analysis to validation in breast cancer.
发表日期:2023
作者:
Ruijun Zhao, Shuanglong Chen, Weiheng Cui, Chaoyu Xie, Aiping Zhang, Li Yang, Hongmei Dong
来源:
Frontiers in Immunology
摘要:
蛋白酪氨酸磷酸酶非受体 1 型 (PTPN1) 是蛋白酪氨酸磷酸酶超家族的成员,已被确定为多种癌症的癌基因和治疗靶点。然而,它在确定人类癌症预后和免疫反应中的确切作用仍然难以捉摸。本研究调查了人类癌症中 PTPN1 表达与临床结果、免疫浸润和药物敏感性之间的关系,这将增进对其在泛癌中的预后价值和免疫学作用的理解。PTPN1 表达谱来自癌症基因组图谱和癌细胞系百科全书数据库。利用Kaplan-Meier、单变量Cox回归和时间依赖性受试者工作特征曲线分析来阐明PTPN1表达与泛癌患者预后之间的关系。使用表达数据和肿瘤免疫估计资源估计恶性肿瘤组织中的基质和免疫细胞,分析 PTPN1 表达与肿瘤浸润免疫细胞的存在之间的关系。采用细胞计数试剂盒8(CCK-8)检测PTPN1水平对乳腺癌细胞对紫杉醇敏感性的影响。采用免疫组织化学和免疫印迹研究人乳腺癌组织和小鼠异种移植模型中PTPN1表达、免疫细胞浸润和免疫检查点基因表达之间的关系。泛癌分析显示PTPN1在多种癌症中频繁上调。 PTPN1 高表达与大多数癌症的不良预后相关。此外,PTPN1的表达与肿瘤浸润免疫细胞的存在以及不同癌症中免疫检查点通路标记基因的表达高度相关。此外,PTPN1 显着预测接受免疫治疗的患者的预后。 CCK-8活力测定的结果表明,PTPN1敲除增加了MDA-MB-231和MCF-7细胞对紫杉醇的敏感性。最后,我们的结果表明,PTPN1与乳腺癌中的免疫浸润和免疫检查点基因表达相关。PTPN1在多种癌症类型中过表达,并与临床结果和肿瘤免疫相关,表明它可能是一种有价值的潜在预后和免疫学生物标志物。 pan-cancer.版权所有 © 2023 赵、陈、崔、谢、张、杨和董。
Protein tyrosine phosphatase non-receptor type 1 (PTPN1), a member of the protein tyrosine phosphatase superfamily, has been identified as an oncogene and therapeutic target in various cancers. However, its precise role in determining the prognosis of human cancer and immunological responses remains elusive. This study investigated the relationship between PTPN1 expression and clinical outcomes, immune infiltration, and drug sensitivity in human cancers, which will improve understanding regarding its prognostic value and immunological role in pan-cancer.The PTPN1 expression profile was obtained from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia databases. Kaplan-Meier, univariate Cox regression, and time-dependent receiver operating characteristic curve analyses were utilized to clarify the relationship between PTPN1 expression and the prognosis of pan-cancer patients. The relationships between PTPN1 expression and the presence of tumor-infiltrated immune cells were analyzed using Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data and Tumor Immune Estimation Resource. The cell counting kit-8 (CCK-8) assay was performed to examine the effects of PTPN1 level on the sensitivity of breast cancer cells to paclitaxel. Immunohistochemistry and immunoblotting were used to investigate the relationship between PTPN1 expression, immune cell infiltration, and immune checkpoint gene expression in human breast cancer tissues and a mouse xenograft model.The pan-cancer analysis revealed that PTPN1 was frequently up-regulated in various cancers. High PTPN1 expression was associated with poor prognosis in most cancers. Furthermore, PTPN1 expression correlated highly with the presence of tumor-infiltrating immune cells and the expression of immune checkpoint pathway marker genes in different cancers. Furthermore, PTPN1 significantly predicted the prognosis for patients undergoing immunotherapy. The results of the CCK-8 viability assay revealed that PTPN1 knockdown increased the sensitivity of MDA-MB-231 and MCF-7 cells to paclitaxel. Finally, our results demonstrated that PTPN1 was associated with immune infiltration and immune checkpoint gene expression in breast cancer.PTPN1 was overexpressed in multiple cancer types and correlated with the clinical outcome and tumor immunity, suggesting it could be a valuable potential prognostic and immunological biomarker for pan-cancer.Copyright © 2023 Zhao, Chen, Cui, Xie, Zhang, Yang and Dong.