Related Experiment Videos
Elevated PTK6 expression is associated with tumor immune microenvironment remodeling and predicts poor prognosis in
Zebiao Ma1,2, Jiongyu Chen3, Lihua Tang1
1Department of Gynecologic Oncology, Guangdong Engineering Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics (Proposed)/GuangDong Engineering Technology Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics, Cancer Hospital of Shantou University Medical College, Shantou, China.
Background:
Uterine corpus endometrial carcinoma (UCEC) incidence rises globally, with >50% of advanced/recurrent patients showing poor response to immune checkpoint inhibitors due to inadequate biomarkers. Protein tyrosine kinase 6 (PTK6), aberrantly expressed in malignancies and linked to tumor progression, lacks defined clinical significance in UCEC.
Methods:
Multi-omics analysis utilized UCEC RNA-seq (TCGA/GEO) and proteomics (CPTAC). PTK6 protein interactors from STRING were used for functional enrichment analysis. Tumor microenvironment (TME) was assessed via ESTIMATE (stromal/immune scores), TIMER3 (immune infiltration), and TCIA (immunophenoscore, IPS). Immunohistochemistry (IHC) validation (n = 200) explored the prognostic value.
Results:
PTK6 was upregulated in UCEC (p < 0.001) with promoter hypomethylation (median β: 0.32 vs. normal 0.52, p < 0.001), highest in microsatellite instability-high (MSI-H) subtype, and correlated with tumor mutational burden (TMB). High PTK6 expression associated with worse overall survival (OS) in both entire cohort (HR = 2.065, 95% CI 1.060-4.203, p = 0.033) and MSI-H subtype (HR = 8.562, 95% CI 2.226-32.930, p = 0.0018). Exploratory analysis suggested low PTK6-linked reduced progression-free survival in POLE subtype (HR = 10.48, 95% CI 1.063-103.4, p = 0.044; wide CI suggests caution). PTK6-related genes were mainly involved in ERBB signaling, PD-1/PD-L1 immune checkpoint in cancers, and focal adhesion. Upregulated PTK6 was associated with an altered TME (increased neutrophils, decreased CD8+ T cells, reduced IPS; all p < 0.05). IHC confirmed PTK6 overexpression as an independent poor prognostic factor for OS (HR = 5.050, 95% CI 2.136-11.943, p < 0.001), associating with aggressive clinicopathological features (all p < 0.05).
Conclusion:
PTK6 represents a context-dependent prognostic biomarker linked to tumor immune microenvironment remodeling in UCEC, suggesting its potential utility for immunotherapeutic optimization.
Related Concept Videos
02:17The Tumor Microenvironment
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...