A Novel Composite Biomarker Panel For Detection Of Early Stage Non-small Cell Lung Cancer.

IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Eric L R Bedard, Aswin G Abraham, Anil A Joy, Sunita Ghosh, Xiaoyu Wang, Andrew Lim, Dongyu Shao, Raimar Loebenberg, Wilson H Roa
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引用次数: 2

Abstract

Purpose: To investigate a novel composite methodology of using targeted serum microRNAs (micro ribonucleic acid; miRNA) and urine metabolites for the accurate detection of early stage non-small cell lung cancer (NSCLC).

Methods: Consecutively consenting NSCLC patients and matched control subjects were recruited to provide samples of serum for miRNA and/or urine for metabolite analyses. Serum miRNA levels were measured using quantitative real-time reverse-transcription with exogenous control, and the comparative delta cycle threshold (CT) method was used to calculate relative miRNA expression of two targeted miRNAs (miR-21 and miR-223). The concentrations of six targeted urinary metabolites in patients and healthy controls were measured using proton nuclear magnetic resonance (1H NMR) spectroscopy. A composite methodology of using the 35 accruals with both serum and urine biomarkers was then established with binary logistic regression, receiver operating characteristic (ROC) models with or without artificial intelligence (AI).

Results: The ROC analysis of miRNA expression yielded a sensitivity of 96.4% and a specificity of 88.2% for the detection of early stage NSCLC, with area under the curve (AUC) = 0.91 (CI 95%: 0.80-1.0). Relative urinary concentrations of 4-methoxyphenylacetic acid (4MPLA) were significantly different between NSCLC and healthy control (p=0.008). The ROC analysis of 4MPLA yielded a sensitivity of 82.1% and a specificity of 88.2%, with AUC = 0.85. The composite process combining miRNA and metabolite expression demonstrated a sensitivity and specificity of nearly 100% and AUC=1.

Conclusions: A highly specific, sensitive and non-invasive detection method for NSCLC was developed. Pending validation, this can potentially improve the early detection and, hence, the treatment and survival outcomes of patients.

一种检测早期非小细胞肺癌的新型复合生物标志物面板。
目的:研究一种靶向血清microrna(微核糖核酸;miRNA)和尿液代谢物用于早期非小细胞肺癌(NSCLC)的准确检测。方法:连续招募同意的非小细胞肺癌患者和匹配的对照受试者,提供血清样本用于miRNA和/或尿液样本用于代谢物分析。采用外源对照的实时定量反转录法测定血清miRNA水平,并采用比较δ周期阈值(CT)法计算两种靶向miRNA (miR-21和miR-223)的相对miRNA表达量。采用质子核磁共振(1H NMR)波谱法测定患者和健康对照者6种目标尿液代谢物的浓度。然后利用二元逻辑回归、受试者工作特征(ROC)模型(有或没有人工智能(AI))建立了一种综合方法,将35项应计指标与血清和尿液生物标志物一起使用。结果:miRNA表达的ROC分析对早期NSCLC检测的敏感性为96.4%,特异性为88.2%,曲线下面积(AUC) = 0.91 (CI 95%: 0.80-1.0)。非小细胞肺癌患者尿中4-甲氧基苯乙酸(4MPLA)相对浓度与健康对照组差异有统计学意义(p=0.008)。4MPLA的ROC分析灵敏度为82.1%,特异性为88.2%,AUC = 0.85。结合miRNA和代谢物表达的复合过程的敏感性和特异性接近100%,AUC=1。结论:建立了一种特异性高、灵敏度高、无创的非小细胞肺癌检测方法。在验证之前,这可能会改善早期发现,从而改善患者的治疗和生存结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical and Investigative Medicine
Clinical and Investigative Medicine 医学-医学:研究与实验
CiteScore
1.50
自引率
12.50%
发文量
18
审稿时长
>12 weeks
期刊介绍: Clinical and Investigative Medicine (CIM), publishes original work in the field of Clinical Investigation. Original work includes clinical or laboratory investigations and clinical reports. Reviews include information for Continuing Medical Education (CME), narrative review articles, systematic reviews, and meta-analyses.
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