Qin Rujia, Peng Wen, Wang Xuemin, Li Chunyan, Xi Yan, Zhong Zhaoming, Sun Chuanzheng
Department of Head and Neck Surgery Section II, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China.
Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Oncol. 2021 May 28;11:615963. doi: 10.3389/fonc.2021.615963. eCollection 2021.
Cutaneous melanoma (CM) is the leading cause of skin cancer deaths and is typically diagnosed at an advanced stage, resulting in a poor prognosis. The tumor microenvironment (TME) plays a significant role in tumorigenesis and CM progression, but the dynamic regulation of immune and stromal components is not yet fully understood. In the present study, we quantified the ratio between immune and stromal components and the proportion of tumor-infiltrating immune cells (TICs), based on the ESTIMATE and CIBERSORT computational methods, in 471 cases of skin CM (SKCM) obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were analyzed by univariate Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis to identify prognosis-related genes. The developed prognosis model contains ten genes, which are all vital for patient prognosis. The areas under the curve (AUC) values for the developed prognostic model at 1, 3, 5, and 10 years were 0.832, 0.831, 0.880, and 0.857 in the training dataset, respectively. The GSE54467 dataset was used as a validation set to determine the predictive ability of the prognostic signature. Protein-protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were used to verify "real" hub genes closely related to the TME. These hub genes were verified for differential expression by immunohistochemistry (IHC) analyses. In conclusion, this study might provide potential diagnostic and prognostic biomarkers for CM.
皮肤黑色素瘤(CM)是皮肤癌死亡的主要原因,通常在晚期被诊断出来,预后较差。肿瘤微环境(TME)在肿瘤发生和CM进展中起着重要作用,但免疫和基质成分的动态调节尚未完全了解。在本研究中,我们基于ESTIMATE和CIBERSORT计算方法,对从癌症基因组图谱(TCGA)数据库获得的471例皮肤CM(SKCM)病例中的免疫和基质成分比例以及肿瘤浸润免疫细胞(TICs)的比例进行了量化。通过单变量Cox回归分析、最小绝对收缩和选择算子(LASSO)回归分析以及多变量Cox回归分析来分析差异表达基因(DEGs),以确定预后相关基因。所建立的预后模型包含十个基因,这些基因对患者预后都至关重要。在训练数据集中,所建立的预后模型在1、3、5和10年时的曲线下面积(AUC)值分别为0.832、0.831、0.880和0.857。使用GSE54467数据集作为验证集来确定预后特征的预测能力。蛋白质-蛋白质相互作用(PPI)分析和加权基因共表达网络分析(WGCNA)用于验证与TME密切相关的“真正”枢纽基因。通过免疫组织化学(IHC)分析验证了这些枢纽基因的差异表达。总之,本研究可能为CM提供潜在的诊断和预后生物标志物。