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A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients.

ABSTRACT: Circulating microRNAs (miRNAs) are promising biomarkers for cancer detection. However, multiethnic and multicentric studies of non-small-cell lung cancer (NSCLC) are lacking. We recruited 221 NSCLC patients, 161 controls and 56 benign nodules from both China and America. Initial miRNA screening was performed using the TaqMan Low Density Array followed by confirming individually by RT-qPCR in Chinese cohorts. Finally, we performed a blind trial from an American cohort to validate our findings. RT-qPCR confirmed that miR-483-5p, miR-193a-3p, miR-25, miR-214 and miR-7 were significantly elevated in patients compared to controls. The areas under the curve (AUCs) of the ROC curve of this five-serum miRNA panel were 0.976 (95% CI, 0.939-1.0; P < 0.0001) and 0.823 (95% CI, 0.75-0.896; P < 0.0001) for the two confirmation sets, respectively. In the blind trial, the panel correctly classified 95% NSCLC cases and 84% controls from the American cohort. Most importantly, the panel was capable of distinguishing NSCLC from benign nodules with an AUC of 0.979 (95% CI, 0.959-1.0) in the American cohort and allowed correct prediction of 86% and 95% stage I-II tumors in the Chinese and American cohorts, respectively. This serum miRNA panel holds the potential for diagnosing ethnically diverse NSCLC patients.

SUBMITTER: Wang C

PROVIDER: S-EPMC4634198 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients.

Wang Cheng C Ding Meng M Xia Mingde M Chen Sidi S Van Le Anh A Soto-Gil Rafael R Shen Yi Y Wang Nan N Wang Junjun J Gu Wanjian W Wang Xiangdong X Zhang Yanni Y Zen Ke K Chen Xi X Zhang Chunni C Zhang Chen-Yu CY

EBioMedicine 20150804 10

Circulating microRNAs (miRNAs) are promising biomarkers for cancer detection. However, multiethnic and multicentric studies of non-small-cell lung cancer (NSCLC) are lacking. We recruited 221 NSCLC patients, 161 controls and 56 benign nodules from both China and America. Initial miRNA screening was performed using the TaqMan Low Density Array followed by confirming individually by RT-qPCR in Chinese cohorts. Finally, we performed a blind trial from an American cohort to validate our findings. RT ...[more]

PMID: 26629532

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Project description:BackgroundLittle is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs).MethodsStudy participants (N = 1264) were counseled and tested with a 25- or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA).ResultsThe mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high- and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High- and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences.ConclusionsIn a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds.Lay summaryMultigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

Project description:BackgroundCirculating microRNAs (miRNAs) have been implicated as novel biomarkers for gastric cancer (GC) diagnosis. However, the mixture of GC subtypes may have led to the inconsistent circulating miRNA profiles, and the clinical performance of circulating miRNAs has not yet been evaluated independently on early detection of GC.MethodsA four-phase study was designed with a total of 160 cancer-free controls, 124 patients with gastric non-cardia adenocarcinoma (GNCA) and 36 patients diagnosed gastric cardia adenocarcinoma (GCA). In the discovery phase, we screened the miRNA expression profile in plasma of 40 GNCA patients (stage I) and 40 matched controls by TaqMan low density array (TLDA) chips with pooled samples. Differentially expressed miRNAs were further validated in individual sample using quantitative reverse-transcriptase PCR (qRT-PCR) in the training phase. Subsequently, in an independent validation phase, the identified miRNAs were evaluated in 48 GNCA patients (stage I) and 102 matched controls. Finally, the identified miRNAs were further assessed in an external validation phase including advanced GNCA and GCA patients. Additionally, the expression levels of identified miRNAs were measured in the media of BGC823 and MGC803 cell lines.ResultsFive miRNAs (miR-16, miR-25, miR-92a, miR-451 and miR-486-5p) showed consistently elevated levels in plasma of the GC patients as compared with controls, and were identified to be potential markers for GNCA with area under the receiver operating characteristic (ROC) curves (AUCs) ranging from 0.850 to 0.925 and 0.694 to 0.790 in the training and validation phases, respectively. The five-miRNA panel presented a high diagnostic accuracy for the early-stage GNCA (AUCs=0.989 and 0.812 for the training and validation phases, respectively). Three miRNAs (miR-16, miR-25 and miR-92a) were excreted into the culture media of GC cell lines.ConclusionsThe five-miRNA panel in plasma may serve as a potential non-invasive biomarker in detecting the early-stage GC.

Dataset Information

A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients.

Publications

A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients.

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