Niu Yanyan, Liu Xiaoyu, Shi Aixiu, Tang Danli, Yao Xiaodong, Lu Yan
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Dermatology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, China.
Front Oncol. 2025 Jul 30;15:1555302. doi: 10.3389/fonc.2025.1555302. eCollection 2025.
Cutaneous melanoma (CM) is a highly malignant tumor originating from melanocytes. Rising incidence rates pose a significant burden on global health and economy. Advanced CM patients face poor prognosis due to high recurrence and treatment resistance. Identifying new prognostic biomarkers and therapeutic targets is crucial for personalized interventions. This study focused on protein tyrosine kinase 6 (PTK6), whose role in CM remains unclear.
To overcome these limitations, this study focused on PTK6 and integrated CM transcriptomic and clinical data from TCGA and GEO databases. Bioinformatics analysis evaluated PTK6 expression and its impact on prognosis. GO and KEGG analyses explored biological functions of PTK6-related differentially expressed genes (DEGs). A prognostic risk score model was constructed and validated based on DEGs, and immune cell infiltration, tumor mutation burden (TMB), chemotherapy drug sensitivity, and immunotherapy response were analyzed. Additionally, regulatory mechanisms of PTK6 were explored through mRNA-miRNA-lncRNA and protein interaction networks. Furthermore, experiments validated PTK6's biological functions.
The results showed that PTK6 was significantly upregulated in CM, and its high expression was closely associated with a decreased overall survival of patients. Enrichment analysis suggested that PTK6-related differentially expressed genes were mainly involved in epidermal development, keratinocyte differentiation, and the IL-17 signaling pathway. The prognostic model constructed based on 11 characteristic genes could effectively distinguish between high- and low-risk patients, showing improvements in prognostic accuracy. Patients in the high-risk group had significantly worse prognosis and higher TMB levels. The low-risk group was more sensitive to various chemotherapy drugs, and most immune checkpoint genes were negatively correlated with prognostic genes. TIDE analysis showed that patients in the high-risk group had a higher potential responsiveness to immunotherapy. Regulatory network analysis identified key miRNAs, lncRNAs, and transcription factors related to PTK6. In vitro experiments further confirmed that high expression of PTK6 promoted the proliferation, invasion, and migration of melanoma cells, and its enzymatic active site played an important regulatory role in the above functions.
The experimental results demonstrate that PTK6 is a novel prognostic biomarker and potential therapeutic target for CM, highlighting its strong potential for real-world clinical applications.This study provides a theoretical basis for understanding PTK6's role in CM and its application in personalized treatment. However, further large-scale, multi-center studies are needed to verify its mechanistic role and clinical value.
皮肤黑色素瘤（CM）是一种起源于黑素细胞的高度恶性肿瘤。发病率的上升给全球健康和经济带来了重大负担。晚期CM患者由于高复发率和治疗耐药性，预后较差。识别新的预后生物标志物和治疗靶点对于个性化干预至关重要。本研究聚焦于蛋白酪氨酸激酶6（PTK6），其在CM中的作用尚不清楚。
为克服这些局限性，本研究聚焦于PTK6，并整合了来自TCGA和GEO数据库的CM转录组和临床数据。生物信息学分析评估了PTK6的表达及其对预后的影响。GO和KEGG分析探索了PTK6相关差异表达基因（DEGs）的生物学功能。基于DEGs构建并验证了预后风险评分模型，并分析了免疫细胞浸润、肿瘤突变负荷（TMB）、化疗药物敏感性和免疫治疗反应。此外，通过mRNA-miRNA-lncRNA和蛋白质相互作用网络探索了PTK6的调控机制。此外，实验验证了PTK6的生物学功能。
结果表明，PTK6在CM中显著上调，其高表达与患者总生存期降低密切相关。富集分析表明，PTK6相关差异表达基因主要参与表皮发育、角质形成细胞分化和IL-17信号通路。基于11个特征基因构建的预后模型能够有效区分高风险和低风险患者，显示出预后准确性的提高。高风险组患者的预后明显更差，TMB水平更高。低风险组对各种化疗药物更敏感，大多数免疫检查点基因与预后基因呈负相关。TIDE分析表明，高风险组患者对免疫治疗的潜在反应性更高。调控网络分析确定了与PTK6相关的关键miRNA、lncRNA和转录因子。体外实验进一步证实，PTK6的高表达促进了黑色素瘤细胞的增殖、侵袭和迁移，其酶活性位点在上述功能中发挥了重要的调控作用。
实验结果表明，PTK6是CM的一种新型预后生物标志物和潜在治疗靶点，突出了其在实际临床应用中的强大潜力。本研究为理解PTK6在CM中的作用及其在个性化治疗中的应用提供了理论依据。然而，需要进一步的大规模、多中心研究来验证其机制作用和临床价值。
