Vykoukal Jody, Fahrmann Johannes F, Patel Nikul, Shimizu Masayoshi, Ostrin Edwin J, Dennison Jennifer B, Ivan Cristina, Goodman Gary E, Thornquist Mark D, Barnett Matt J, Feng Ziding, Calin George A, Hanash Samir M
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2022 Aug 30;14(17):4221. doi: 10.3390/cancers14174221.
There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed for their predictive performance in identifying lung cancer cases in the pre-diagnostic setting. The 30 miRNAs were assayed using sera collected from 102 individuals diagnosed with lung cancer within one year following blood draw and 212 controls matched for age, sex, and smoking status. The additive performance of top-performing miRNA candidates in combination with a previously validated four-protein marker panel (4MP) consisting of the precursor form of surfactant protein B (Pro-SFTPB), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA21-1) was additionally assessed. Of the 30 miRNAs evaluated, five (miR-320a-3p, miR-210-3p, miR-92a-3p, miR-21-5p, and miR-140-3p) were statistically significantly (Wilcoxon rank sum test p < 0.05) elevated in case sera compared to controls, with individual AUCs ranging from 0.57−0.62. Compared to the 4MP alone, the combination of 3-miRNAs + 4MP improved sensitivity at 95% specificity by 19.1% ((95% CI of difference 0.0−28.6); two-sided p: 0.006). Our findings demonstrate utility for miRNAs for early detection of lung cancer in combination with a four-protein marker panel.
开发循环生物标志物以实现肺癌的早期检测，从而能够在有更有效治疗选择时更早地拦截肺癌，这一需求尚未得到满足。在此，我们对从已发表文献综述中挑选出的一组30种miRNA进行了评估，以确定它们在诊断前环境中识别肺癌病例的预测性能。使用在采血后一年内被诊断为肺癌的102名个体以及年龄、性别和吸烟状况相匹配的212名对照者的血清对这30种miRNA进行检测。此外，还评估了表现最佳的miRNA候选物与先前验证的由表面活性蛋白B前体形式（Pro-SFTPB）、癌抗原125（CA125）、癌胚抗原（CEA）和细胞角蛋白19片段（CYFRA21-1）组成的四蛋白标志物组（4MP）联合使用时的附加性能。在评估的30种miRNA中，有5种（miR-320a-3p、miR-210-3p、miR-92a-3p、miR-21-5p和miR-140-3p）在病例血清中与对照相比有统计学显著升高（Wilcoxon秩和检验p<0.05），个体AUC范围为0.57 - 0.62。与单独使用4MP相比，3种miRNA + 4MP的组合在95%特异性时将灵敏度提高了19.1%（差异的95%CI为0.0 - 28.6；双侧p：0.006）。我们的研究结果证明了miRNA与四蛋白标志物组联合用于肺癌早期检测的实用性。
