Branca Mattia, Orso Samuel, Molinari Roberto C, Xu Haotian, Guerrier Stéphane, Zhang Yuming, Mili Nabil
Research Center for Statistics, Geneva School of Economics and Management, University of Geneva, Geneva, Switzerland.
Department of Statistics and Institute for CyberScience, Eberly College of Science, Pennsylvania State University, State College, Pennsylvania, USA.
Melanoma Res. 2018 Feb;28(1):21-29. doi: 10.1097/CMR.0000000000000412.
Cutaneous melanoma is a highly aggressive skin cancer whose treatment and prognosis are critically affected by the presence of metastasis. In this study, we address the following issue: which gene transcripts and what kind of interactions between them can allow to predict nonmetastatic from metastatic melanomas with a high level of accuracy? We carry out a meta-analysis on the first gene expression set of the Leeds melanoma cohort, as made available online on 11 May 2016 through the ArrayExpress platform with MicroArray Gene Expression number 4725. According to the authors, primary melanoma mRNA expression was measured in 204 tumours using an illumina DASL HT12 4 whole-genome array. The tumour transcripts were selected through a recently proposed predictive-based regression algorithm for gene-network selection. A set of 64 equivalent models, each including only two gene transcripts, were each sufficient to accurately classify primary tumours into metastatic and nonmetastatic melanomas. The sensitivity and specificity of the genomic-based models were, respectively, 4% (95% confidence interval: 0.11-21.95%) and 99% (95% confidence interval: 96.96-99.99%). The very high specificity coupled with a significantly large positive likelihood ratio leads to a conclusive increase in the likelihood of disease when these biomarkers are present in the primary tumour. In conjunction with other highly sensitive methods, this approach can aspire to be part of the future standard diagnosis methods for the screening of metastatic cutaneous melanoma. The small dimension of the selected transcripts models enables easy handling of large-scale genomic testing procedures. Moreover, some of the selected transcripts have an understandable link with what is known about cutaneous melanoma oncogenesis, opening a window on the molecular pathways underlying the metastatic process of this disease.
皮肤黑色素瘤是一种侵袭性很强的皮肤癌,其治疗和预后会受到转移情况的严重影响。在本研究中,我们探讨以下问题:哪些基因转录本以及它们之间的何种相互作用能够以高度准确性预测非转移性黑色素瘤与转移性黑色素瘤?我们对利兹黑色素瘤队列的首个基因表达数据集进行了荟萃分析,该数据集于2016年5月11日通过ArrayExpress平台在线提供,微阵列基因表达编号为4725。据作者称,使用Illumina DASL HT12 4全基因组阵列在204个肿瘤中测量了原发性黑色素瘤的mRNA表达。通过最近提出的基于预测的回归算法进行基因网络选择来筛选肿瘤转录本。一组64个等效模型,每个模型仅包含两个基因转录本,每个模型都足以将原发性肿瘤准确分类为转移性和非转移性黑色素瘤。基于基因组的模型的敏感性和特异性分别为4%(95%置信区间:0.11 - 21.95%)和99%(95%置信区间:96.96 - 99.99%)。当这些生物标志物存在于原发性肿瘤中时,极高的特异性加上显著大的阳性似然比导致疾病可能性的决定性增加。与其他高灵敏度方法相结合,这种方法有望成为未来筛查转移性皮肤黑色素瘤的标准诊断方法的一部分。所选转录本模型的小尺寸使得大规模基因组检测程序易于处理。此外,一些所选转录本与已知的皮肤黑色素瘤肿瘤发生过程有可理解的联系,为该疾病转移过程的分子途径打开了一扇窗。