Scholarlink

Background <p>Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by a dismal prognosis and limited treatment options. Protein tyrosine kinase 6 (PTK6) is abnormally activated in multiple cancer types. Understanding the function of PTK6 in pancreatic cancer could reveal novel therapeutic targets and prognostic markers.</p> Methods <p>We extracted the expression profiles and clinical data of patients with pancreatic adenocarcinoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The Wilcoxon rank-sum test was used to compare PTK6 gene expression levels between tumor tissues and normal pancreatic tissues. Functional enrichment analysis, Cox regression analysis, and Kaplan–Meier plot analysis were employed to determine the prognostic value of PTK6. Single-sample gene set enrichment analysis (ssGSEA) and TIMER3.0 were used to evaluate immune cell infiltration. Finally, CCK-8, RT‒qPCR, colony formation, and western blot assays were performed in vitro cellular experiments to verify the biological effects of PTK6 on the malignant behaviour of pancreatic cancer.</p> Results <p>PTK6 is highly expressed in pancreatic adenocarcinoma, with its upregulation validated in both TCGA (AUC = 0.935) and GEO (AUC = 0.796) cohorts. Elevated PTK6 expression was correlated with shorter overall survival (HR = 2.08, 95% CI: 1.36–3.19, <i>p</i> &lt; 0.001), and multivariate analysis revealed that N1 stage was an independent prognostic factor for OS. In addition, PTK6 expression was negatively correlated with immune cell infiltration and key immune checkpoint genes, with the strongest correlation observed for TIGIT (ρ = -0.316, <i>p</i> &lt; 0.001). In vitro experiments revealed that downregulating PTK6 expression via siRNA inhibited cell proliferation and colony formation, concomitant with increased LC3-II/LC3-I ratio, suggesting a potential role in autophagy regulation.</p> Conclusion <p>PTK6 could serve as a potential diagnostic and prognostic biomarker for PAAD and may participate in immune modulation and autophagy regulation. These findings, supported by multi-cohort bioinformatic analysis and preliminary experimental validation, highlight its prospective clinical value in prognosis evaluation, immunotherapy, and targeted therapy for PAAD.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Role of PTK6 in the diagnosis, prognosis, and immune infiltration of pancreatic cancer based on evidence from bioinformatics analysis and experimental validation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月28日

查看全文
  • Feng-jiao Wang,
  • Shu-lin Yu,
  • Pei-wen Yang,
  • Ju-ying Jiao,
  • Feng-gang Hou,
  • Yue Fan

摘要

Background

Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by a dismal prognosis and limited treatment options. Protein tyrosine kinase 6 (PTK6) is abnormally activated in multiple cancer types. Understanding the function of PTK6 in pancreatic cancer could reveal novel therapeutic targets and prognostic markers.

Methods

We extracted the expression profiles and clinical data of patients with pancreatic adenocarcinoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The Wilcoxon rank-sum test was used to compare PTK6 gene expression levels between tumor tissues and normal pancreatic tissues. Functional enrichment analysis, Cox regression analysis, and Kaplan–Meier plot analysis were employed to determine the prognostic value of PTK6. Single-sample gene set enrichment analysis (ssGSEA) and TIMER3.0 were used to evaluate immune cell infiltration. Finally, CCK-8, RT‒qPCR, colony formation, and western blot assays were performed in vitro cellular experiments to verify the biological effects of PTK6 on the malignant behaviour of pancreatic cancer.

Results

PTK6 is highly expressed in pancreatic adenocarcinoma, with its upregulation validated in both TCGA (AUC = 0.935) and GEO (AUC = 0.796) cohorts. Elevated PTK6 expression was correlated with shorter overall survival (HR = 2.08, 95% CI: 1.36–3.19, p < 0.001), and multivariate analysis revealed that N1 stage was an independent prognostic factor for OS. In addition, PTK6 expression was negatively correlated with immune cell infiltration and key immune checkpoint genes, with the strongest correlation observed for TIGIT (ρ = -0.316, p < 0.001). In vitro experiments revealed that downregulating PTK6 expression via siRNA inhibited cell proliferation and colony formation, concomitant with increased LC3-II/LC3-I ratio, suggesting a potential role in autophagy regulation.

Conclusion

PTK6 could serve as a potential diagnostic and prognostic biomarker for PAAD and may participate in immune modulation and autophagy regulation. These findings, supported by multi-cohort bioinformatic analysis and preliminary experimental validation, highlight its prospective clinical value in prognosis evaluation, immunotherapy, and targeted therapy for PAAD.