Center for Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.
Centre for Systems Biology and Bioinformatics, Panjab University, Chandigarh, India.
Sci Rep. 2019 Oct 31;9(1):15790. doi: 10.1038/s41598-019-52134-4.
The metastatic Skin Cutaneous Melanoma (SKCM) has been associated with diminished survival rates and high mortality rates worldwide. Thus, segregating metastatic melanoma from the primary tumors is crucial to employ an optimal therapeutic strategy for the prolonged survival of patients. The SKCM mRNA, miRNA and methylation data of TCGA is comprehensively analysed to recognize key genomic features that can segregate metastatic and primary tumors. Further, machine learning models have been developed using selected features to distinguish the same. The Support Vector Classification with Weight (SVC-W) model developed using the expression of 17 mRNAs achieved Area under the Receiver Operating Characteristic (AUROC) curve of 0.95 and an accuracy of 89.47% on an independent validation dataset. This study reveals the genes C7, MMP3, KRT14, LOC642587, CASP7, S100A7 and miRNAs hsa-mir-205 and hsa-mir-203b as the key genomic features that may substantially contribute to the oncogenesis of melanoma. Our study also proposes genes ESM1, NFATC3, C7orf4, CDK14, ZNF827, and ZSWIM7 as novel putative markers for cutaneous melanoma metastasis. The major prediction models and analysis modules to predict metastatic and primary tumor samples of SKCM are available from a webserver, CancerSPP ( http://webs.iiitd.edu.in/raghava/cancerspp/ ).
转移性皮肤黑色素瘤(SKCM)与全球范围内生存率降低和死亡率升高有关。因此,将转移性黑色素瘤与原发性肿瘤区分开来,对于为患者的长期生存采用最佳治疗策略至关重要。TCGA 的 SKCM mRNA、miRNA 和甲基化数据被全面分析,以识别可区分转移性和原发性肿瘤的关键基因组特征。此外,还使用选定的特征开发了机器学习模型来进行区分。使用 17 个 mRNA 表达开发的支持向量分类与加权(SVC-W)模型在独立验证数据集上实现了 0.95 的接收器操作特征(AUROC)曲线下面积和 89.47%的准确性。这项研究揭示了基因 C7、MMP3、KRT14、LOC642587、CASP7、S100A7 和 miRNA hsa-mir-205 和 hsa-mir-203b 作为可能对黑色素瘤发生有重大贡献的关键基因组特征。我们的研究还提出了 ESM1、NFATC3、C7orf4、CDK14、ZNF827 和 ZSWIM7 等基因作为皮肤黑色素瘤转移的新潜在标记物。用于预测 SKCM 转移性和原发性肿瘤样本的主要预测模型和分析模块可从一个网络服务器 CancerSPP(http://webs.iiitd.edu.in/raghava/cancerspp/)获得。