Liu Tung, Lin Yu-Chieh, Chang Pei-Chi, Hueng Dueng-Yuan, Li Yao-Feng
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, Republic of China.
Department of Pathology and Laboratory Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, 325, Taiwan, Republic of China.
Discov Oncol. 2025 May 24;16(1):914. doi: 10.1007/s12672-025-02662-5.
Gliomas, particularly IDH-wildtype astrocytomas, remain highly aggressive and resistant to current therapies. Despite advances in molecular classification, effective therapeutic targets are still limited. Consequently, identifying new targets is essential to improve patient survival. PTPN7, a tyrosine phosphatase implicated in MAPK signaling, is known to play roles in various malignancies but remains underexplored in gliomas. This study examines the prognostic significance, spatial distribution, and immune-related functions of PTPN7, aiming to elucidate its potential as a prognostic role and therapeutic target in glioma treatment.
We analyzed PTPN7 mRNA expression in gliomas via TCGA, CGGA, and single-cell RNA sequencing (GSE131928 and GSE89567). Kaplan determined prognostic significance-Meier and uni-/multi-variate Cox survival analyses. Gene set enrichment analysis (GSEA) was used to identify dysregulated pathways, immune signatures, and cell-type enrichments. We also applied CIBERSORT to evaluate the relationships between PTPN7 expression and 12-principal cell states and 22 immune populations. Spatial transcriptomics (Ivy Glioblastoma Atlas, 10 × Genomics Visium) mapped PTPN7 distribution; these findings were corroborated by immunohistochemistry-validated protein expression in 70 cases.
Pan-cancer analysis revealed PTPN7 overexpression in multiple malignancies, including glioma. Notably, PTPN7 was significantly elevated in IDH-wildtype astrocytomas, correlating with higher tumor grades and poorer overall survival. GSEA indicated that high PTPN7 is linked to T-cell differentiation, macrophage/monocyte activation, and dendritic cell-associated pathways. Both immune deconvolution and single-cell analyses showed that PTPN7 positively correlates with myeloid series and T-cell populations, supported by additional GSEA findings. In the Ivy dataset and spatial transcriptomics, PTPN7 was concentrated in peri-necrotic, cellular tumor, and slightly lower in the infiltrating border regions, consistent with immune interaction sites. Immunohistochemical data further demonstrated high PTPN7 expression tracks with increased tumor grade, reaching statistical significance in IDH-wildtype astrocytomas and confirming its clinical relevance.
This study positions PTPN7 as a prognostic biomarker and immune modulator in gliomas, particularly IDH-wildtype astrocytomas. Its expression correlates with tumor aggressiveness and immune infiltration, potentially driving glioma progression. Targeting PTPN7 may disrupt immune evasion and support tumor eradication, indicating a promising therapeutic avenue in immunotherapy-based strategies.
胶质瘤，尤其是异柠檬酸脱氢酶（IDH）野生型星形细胞瘤，仍然具有高度侵袭性且对当前治疗有抗性。尽管在分子分类方面取得了进展，但有效的治疗靶点仍然有限。因此，确定新的靶点对于提高患者生存率至关重要。蛋白酪氨酸磷酸酶非受体型7（PTPN7）是一种参与丝裂原活化蛋白激酶（MAPK）信号传导的酪氨酸磷酸酶，已知在各种恶性肿瘤中发挥作用，但在胶质瘤中的研究仍不充分。本研究探讨PTPN7的预后意义、空间分布及免疫相关功能，旨在阐明其在胶质瘤治疗中作为预后标志物和治疗靶点的潜力。
我们通过癌症基因组图谱（TCGA）、中国胶质瘤基因组图谱（CGGA）以及单细胞RNA测序（基因表达综合数据库GSE131928和GSE89567）分析胶质瘤中PTPN7 mRNA的表达。采用Kaplan-Meier法和单因素/多因素Cox生存分析确定预后意义。基因集富集分析（GSEA）用于识别失调的信号通路、免疫特征和细胞类型富集情况。我们还应用CIBERSORT评估PTPN7表达与12种主要细胞状态和22种免疫细胞群体之间的关系。空间转录组学（常春藤胶质母细胞瘤图谱，10×基因组学Visium平台）绘制PTPN7的分布图；70例病例的免疫组化验证蛋白表达结果证实了这些发现。
泛癌分析显示PTPN7在包括胶质瘤在内的多种恶性肿瘤中过表达。值得注意的是，PTPN7在IDH野生型星形细胞瘤中显著升高，与更高的肿瘤分级和更差的总生存期相关。GSEA表明高PTPN7水平与T细胞分化、巨噬细胞/单核细胞活化以及树突状细胞相关信号通路有关。免疫反卷积和单细胞分析均显示PTPN7与髓系细胞和T细胞群体呈正相关，GSEA的其他发现也支持这一点。在常春藤数据集和空间转录组学中，PTPN7集中在坏死周边、肿瘤细胞区域，在浸润边缘区域略低，与免疫相互作用位点一致。免疫组化数据进一步表明PTPN7高表达与肿瘤分级增加相关，在IDH野生型星形细胞瘤中具有统计学意义，证实了其临床相关性。
本研究将PTPN7定位为胶质瘤，尤其是IDH野生型星形细胞瘤的预后生物标志物和免疫调节剂。其表达与肿瘤侵袭性和免疫浸润相关，可能推动胶质瘤进展。靶向PTPN7可能会破坏免疫逃逸并有助于肿瘤清除，这表明在基于免疫治疗的策略中是一条有前景的治疗途径。
