Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy

• Published in: European journal of medical research 2024-01, Vol.29 (1), p.12-12, Article 12
• Main Authors: Zhou, Ziting, Lin, Zhengjun, Wang, Mingrui, Wang, Lifan, Ji, Yuqiao, Yang, Jing, Yang, Yaocheng, Zhu, Guanghui, Liu, Tang
• Format: Article
• Language: English
• Subjects: Analysis; B cells; Biomarkers; Breast cancer; Breast Neoplasms; Cancer; Carcinoma, Renal Cell; Dendritic cells; Development and progression; Disease susceptibility; Drug therapy; Ethylenediaminetetraacetic acid; Female; Genetic aspects; Genomics; Humans; Immune Checkpoint Inhibitors; Immunohistochemistry; Immunotherapy; Kidney Neoplasms; Lung cancer; Medical prognosis; Medical research; Medicine, Experimental; Mutation; Ovarian cancer; Phosphatases; Prognosis; Programmed Cell Death 1 Receptor; Protein Tyrosine Phosphatase, Non-Receptor Type 3; Rankings; RNA sequencing; Sarcoma; T cells; Tumor Microenvironment - genetics; Tyrosine
• ISSN: 2047-783X; 0949-2321; 2047-783X
• DOI: 10.1186/s40001-023-01587-5

The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of ca