Lin Zexu, Lin Xin, Sun Yuming, Lei Shaorong, Cai Gengming, Li Zhexuan
Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Department of Plastic and Cosmetic Surgery, First Affiliated Hospital of Quanzhou, Fujian Medical University, Quanzhou, China.
Front Genet. 2023 Jan 26;14:1098202. doi: 10.3389/fgene.2023.1098202. eCollection 2023.
Melanoma is a malignancy of melanocytes, responsible for a high percentage of skin cancer mortality. Ligand-Receptor pairs, a type of cellular communication, are essential for tumor genesis, growth, metastasis, and prognosis. Yet, the role of Ligand-Receptor pairs in melanoma has not been fully elucidated. Our research focused on the function of Ligand-Receptor pairs in melanoma prognosis. We screened 131 melanoma prognosis corresponded ligand-receptor pairs by analyzing the TCGA data of melanoma and the 2293 LR pairs retrieved from the connectomeDB2020 database. And further developed subtypes of melanoma according to the expression of these ligand-receptor pairs by Consensus Clustering. Then we using lasso cox regression and stepwise multivariate regression analysis established a ligand-receptor pairs-based scoring model for the evaluation of melanoma prognosis. Our study demonstrated that the ligand-receptor pairs are vital to the molecular heterogeneity of melanoma, and characterized three different melanoma ligand-receptor pairs subtypes. Among them, the C3 subtype showed a better prognosis, while the C1 subtype exhibited a low prognosis state. And our analysis then found out that this could be related to the differed activation and inhabitation of the cell cycle and immune-related pathways. Using lasso cox regression and stepwise multivariate regression analysis, we further identified 9 key ligand-receptor pairs and established a scoring model that effectively correlated with the prognosis, immune pathways, and therapy of melanoma, showing that the LR.score model was a trustworthy and independent biomarker for melanoma prognosis evaluation. In sum, we found that ligand-receptor pairs are significantly associated with the prognosis and therapy of melanoma. And our ligand-receptor-based scoring model showed potential for the evaluation of melanoma prognosis and immune therapy outcome prediction, which is crucial to the survival for the patients.
黑色素瘤是一种黑素细胞恶性肿瘤，在皮肤癌死亡率中占比很高。配体-受体对作为一种细胞通讯方式，对肿瘤的发生、生长、转移和预后至关重要。然而，配体-受体对在黑色素瘤中的作用尚未完全阐明。我们的研究聚焦于配体-受体对在黑色素瘤预后中的功能。我们通过分析黑色素瘤的TCGA数据以及从connectomeDB2020数据库中检索到的2293对配体-受体对，筛选出131对与黑色素瘤预后相关的配体-受体对。然后通过一致性聚类根据这些配体-受体对的表达进一步划分黑色素瘤亚型。接着我们使用套索cox回归和逐步多元回归分析建立了一个基于配体-受体对的评分模型来评估黑色素瘤预后。我们的研究表明，配体-受体对对于黑色素瘤的分子异质性至关重要，并鉴定出三种不同的黑色素瘤配体-受体对亚型。其中，C3亚型显示出较好的预后，而C1亚型表现出低预后状态。并且我们的分析随后发现这可能与细胞周期和免疫相关途径的不同激活和抑制有关。通过套索cox回归和逐步多元回归分析，我们进一步确定了9个关键的配体-受体对，并建立了一个与黑色素瘤的预后、免疫途径和治疗有效相关的评分模型，表明LR.score模型是用于黑色素瘤预后评估的可靠且独立的生物标志物。总之，我们发现配体-受体对与黑色素瘤的预后和治疗显著相关。并且我们基于配体-受体的评分模型在评估黑色素瘤预后和免疫治疗结果预测方面显示出潜力，这对患者的生存至关重要。
