Sun Rongyao, Wei Shuqiang, Yu Ying, Wang Zhuo, Yao Tonghao, Zhang Yining, Cui Luping, Ma Xu
Department of Plastic and Aesthetic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Department of Burn and Plastic Surgery, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266042, China.
Cancer Cell Int. 2024 Dec 28;24(1):435. doi: 10.1186/s12935-024-03625-6.
Cutaneous melanoma is one of the most invasive and lethal skin malignant tumors. Compared to primary melanoma, metastatic melanoma (MM) presents poorer treatment outcomes and a higher mortality rate. The tumor microenvironment (TME) plays a critical role in MM progression and immunotherapy resistance. This study focuses on the role of the TME-related gene PTPN6 in the prognosis and immunotherapy response of MM.
This study analyzed the RNA-seq and clinical data of MM patients from public databases, employing the ESTIMATE algorithm and bioinformatics tools to identify differentially expressed genes in the TME. PTPN6 was identified as a prognostic biomarker. Its expression and function were validated using in vitro and in vivo experiments. The role of PTPN6 in immune cell infiltration and its association with the JAK2-STAT3 pathway and immunotherapy response were also evaluated.
PTPN6 expression was significantly lower in MM and associated with poor prognosis. In vitro, Overexpression of PTPN6 inhibited proliferation, migration, and invasion, while knockdown reversed these effects. In vivo, PTPN6 overexpression reduced tumor growth. Mechanistically, PTPN6 suppressed JAK2-STAT3 signaling pathway activation. High PTPN6 expression was positively associated with immune cell infiltration, improved immunotherapy response, and reduced PD-L1 expression.
The gene PTPN6, associated with the tumor microenvironment, may serve as a promising prognostic biomarker and therapeutic target for MM.
皮肤黑色素瘤是最具侵袭性和致死性的皮肤恶性肿瘤之一。与原发性黑色素瘤相比，转移性黑色素瘤（MM）的治疗效果较差，死亡率更高。肿瘤微环境（TME）在MM进展和免疫治疗耐药中起关键作用。本研究聚焦于TME相关基因PTPN6在MM预后和免疫治疗反应中的作用。
本研究分析了来自公共数据库的MM患者的RNA测序和临床数据，采用ESTIMATE算法和生物信息学工具来识别TME中的差异表达基因。PTPN6被鉴定为一种预后生物标志物。通过体外和体内实验验证了其表达和功能。还评估了PTPN6在免疫细胞浸润中的作用及其与JAK2-STAT3通路和免疫治疗反应的关联。
PTPN6在MM中的表达显著降低，且与预后不良相关。在体外，PTPN6的过表达抑制了增殖、迁移和侵袭，而敲低则逆转了这些作用。在体内，PTPN6的过表达减少了肿瘤生长。机制上，PTPN6抑制了JAK2-STAT3信号通路的激活。高PTPN6表达与免疫细胞浸润、改善免疫治疗反应和降低PD-L1表达呈正相关。
与肿瘤微环境相关的基因PTPN6可能是MM有前景的预后生物标志物和治疗靶点。
