解偶联蛋白2对皮肤黑色素瘤预后和免疫微环境的影响

Effects of uncoupling protein 2 on prognosis and immune microenvironment of skin cutaneous melanoma

目的:探讨解偶联蛋白2(UCP2)在皮肤黑色素瘤(SKCM)中的预后价值,分析UCP2表达与SKCM肿瘤浸润免疫细胞(TIC)之间的相关性。方法:通过GEPIA在线数据库分析SKCM组织及正常皮肤组织中UCP的差异性表达,探讨UCP表达与SKCM预后之间的关系。HPA数据库分析UCP2在正常皮肤单细胞中的表达情况,使用TISCH分析UCP2在SKCM中单细胞水平的表达情况。TIMER分析UCP2表达与总SKCM、原发性SKCM和转移性SKCM患者肿瘤微环境(TME)中主要免疫细胞及其标志物的相关性。结果:UCP2在SKCM癌组织中高表达,UCP2高表达患者的OS和DFS均长于低表达患者(均P<0.05)。正常皮肤和SKCM单细胞分析显示,UCP2表达与免疫细胞亚群存在一定的正相关,同时与SKCM中趋化因子、受体、组织相容性复合物、免疫抑制剂和免疫激活剂五类免疫途径密切相关(均P<0.05)。亚组分析结果显示,UCP2高表达与总SKCM和转移性SKCM患者高OS密切相关(均P<0.05)。UCP2表达与总SKCM、原发性SKCM、转移性SKCM患者TME中TIC之间存在明显的正相关(均P<0.05),但是与原发性SKCM相关性相对较弱。UCP2表达水平与3组SKCM患者TME中免疫细胞标志物存在明显的正相关(均P<0.05)。结论:UCP2在SKCM组织中高表达,UCP2与SKCM中TIC呈正相关,是TME中重要的调控因子,与其预后密切相关。

Objective: To investigate the prognostic value of uncoupling protein 2(UCP2) expression in skin cutaneous melanoma(SKCM) and its relationship with tumor infiltrating immune cells(TICs). Methods: GEPIA online dataset was used to explore the differential expression of UCP2 between SKCM and normal skin tissues, and the correlation of UCP with the prognosis of SKCM was further investigated. HPA dataset was used to analyze the UCP2 expression in single cell of normal skin. TISCH was used to analyze the expression of UCP2 in SKCM at single-cell level. TIMER was used to analyze the correlation between the expression of UCP2 and the main immune cells and their markers in the tumor microenvironment(TME) of SKCM, Primary-SKCM and Metastasis-SKCM.Results: UCP2 was highly expressed in SKCM tissues(P<0.05). Higher UCP2 expression were significantly associated with longer overall survival(OS) and disease-free survival(DFS) of SKCM patients(all P<0.05). Single cell analysis of normal skin and SKCM skin showed that there was a certain positive correlation between UCP2 expression and cellular immune cell subsets and that UCP2 was closely related to 5 immune routes(chemokines, receptors, histocompatibility complexes, immunosuppressants and immune activators)(all P<0.05). The subset analysis showed that high UCP2 expression was closely associated with the high OS rate of SKCM and metastatic SKCM patients(all P<0.05). There was a significant positive correlation between UCP2 expression and TICs in the TME of overall SKCM patients, primary SKCM patients and metastatic SKCM patients(all P<0.05), however, the correlation was relatively low in primary SKCM patients. At the same time, the expression of UCP2 was positively correlated with TME immune cell markers in the three groups of SKCM patients. Conclusion: UCP2 is highly expressed in SKCM tissues and positively correlates with TICs in SKCM, which is an important regulatory factor of TME and closely related to the prognosis of SKCM patients.