Guo Jia-Hui, Yin Shan-Shan, Liu Hua, Liu Feng, Gao Feng-Hou
Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Gastroenterology, The Tenth Hospital Affiliated to Tongji University, Shanghai, China.
Ann Transl Med. 2021 May;9(10):857. doi: 10.21037/atm-21-1794.
The incidence of malignant melanoma accounts for only approximately 5% of skin malignant tumors, however, it accounts for 75% of its mortality. Long-chain non-coding RNA (lncRNA) has a wide range of functional activities. Disorders of lncRNAs may lead to the occurrence and development of melanoma, and may also be related to immunotherapy.
The transcriptomic data of primary and metastatic melanoma patients and 331 immune-related genes were downloaded from skin cutaneous melanoma (SKCM) in the The Cancer Genome Atlas (TCGA) database. On this basis, 460 immunologically relevant lncRNAs were identified by constructing a co-expression network of immunogenic genes and lncRNAs in primary and metastatic melanoma patients. Prognostic genes were screened using univariate Cox regression analysis. ROC analysis was performed to evaluate the robustness of the prognostic signature.
Univariate correlation analysis showed that only 3 of the 23 immune-related lncRNAs were at high risk and the rest were at low risk. Signatures of 7 immune-related lncRNAs were identified by multivariate correlation analysis. The clinical correlation analysis showed that the 7 immune-related lncRNAs were associated with the clinical stage of primary and metastatic melanoma. Principal component analysis (PCA) showed that only 7 immune-related lncRNA signals divided tumor patients into high-risk and low-risk groups, while the low-risk group was enriched in the immune system process M13664 and immune response M19817 sets. PPI interaction network analysis showed that 11 G protein-coupled receptors and 6 corresponding ligands in the 2 gene sets affected the tumor microenvironment and were negatively related to the risk of the 7 immune-related lncRNAs. The tumor microenvironment immune cell infiltration analysis also supported the finding that anti-tumor immunity in the low-risk group was stronger than in the high-risk group.
These results indicate that characteristics of the 7 immune-related lncRNAs have prognostic value for melanoma patients and can be used as potential immunotherapy targets.
恶性黑色素瘤的发病率仅占皮肤恶性肿瘤的约5%,但其死亡率却占皮肤恶性肿瘤死亡率的75%。长链非编码RNA(lncRNA)具有广泛的功能活性。lncRNAs的紊乱可能导致黑色素瘤的发生和发展,也可能与免疫治疗有关。
从癌症基因组图谱(TCGA)数据库中的皮肤黑色素瘤(SKCM)下载原发性和转移性黑色素瘤患者的转录组数据以及331个免疫相关基因。在此基础上,通过构建原发性和转移性黑色素瘤患者免疫原性基因与lncRNAs的共表达网络,鉴定出460个免疫相关lncRNAs。使用单变量Cox回归分析筛选预后基因。进行ROC分析以评估预后特征的稳健性。
单变量相关性分析显示,23个免疫相关lncRNAs中只有3个处于高风险,其余处于低风险。通过多变量相关性分析确定了7个免疫相关lncRNAs的特征。临床相关性分析表明,这7个免疫相关lncRNAs与原发性和转移性黑色素瘤的临床分期相关。主成分分析(PCA)显示,仅7个免疫相关lncRNA信号就将肿瘤患者分为高风险和低风险组,而低风险组在免疫系统过程M13664和免疫反应M19817集合中富集。蛋白质-蛋白质相互作用(PPI)网络分析显示,2个基因集中的11个G蛋白偶联受体和6个相应配体影响肿瘤微环境,并且与7个免疫相关lncRNAs的风险呈负相关。肿瘤微环境免疫细胞浸润分析也支持低风险组的抗肿瘤免疫力强于高风险组这一发现。
这些结果表明,7个免疫相关lncRNAs的特征对黑色素瘤患者具有预后价值,可作为潜在的免疫治疗靶点。