miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer

Our plain-English summary of miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer, by K.M. Foss, C. Sima, D. Ugolini, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: K.M. Foss, C. Sima, D. Ugolini, M. Neri, K.E. Allen, G.J. Weiss
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(3):482-8
• Cited by: 243 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: The ability to diagnose non-small cell lung cancer (NSCLC) at an early stage may lead to improved survival. The aim of this study was to identify differentially expressed serum-based microRNAs (miRNAs) between patients with early-stage NSCLC and controls. These miRNAs may serve as biomarkers for NSCLC early detection.

Methods: miRNA profiling was performed on total RNA extracted from serum obtained from 22 individuals (11 controls and 11 patients with early-stage NSCLC). Quantitative polymerase chain reaction (qPCR) was used to validate the profiling results in the discovery set and in a validation set of 31 controls and 22 patients with early-stage NSCLC. Additionally, six matched plasma samples (four NSCLC cases and two controls) and three serum mesothelioma samples were analyzed by qPCR. Receiver operating characteristic curves were generated for each possible combination of the miRNAs measured by qPCR.

Results: The expression of hsa-miR-1254 and hsa-miR-574-5p was significantly increased in the early-stage NSCLC samples with respect to the controls. Receiver operating characteristic curves plotting these two miRNAs were able to discriminate early-stage NSCLC samples from controls with 82% and 77% of sensitivity and specificity, respectively, in the discovery cohort and with 73% and 71% of sensitivity and specificity, respectively, in the validation cohort. The mesothelioma and plasma samples did not seem to classify into either NSCLC or control groups.

Conclusions: Serum miRNAs are differentially expressed between patients with early-stage NSCLC and controls. The utility of miR-1254 and miR-574-5p serum-based biomarkers as minimally invasive screening and triage tools for subsequent diagnostic evaluation warrants additional validation.

In plain English

This laboratory study looked for small RNA molecules (microRNAs) in blood serum that might tell people with early-stage non-small cell lung cancer (NSCLC) apart from people without it. Samples came from the Cancer of RESpiratory Tract biorepository. Controls were healthy people, nearly all with a history of tobacco smoking. The article does not report participants' asbestos exposure. In a discovery group of 11 patients and 11 controls, the authors screened 880 mature microRNAs and chose four candidates. The pair miR-1254 and miR-574-5p separated patients from controls best, with 82% sensitivity and 77% specificity. In a validation group of 22 patients and 31 controls, the pair reached 73% sensitivity and 71% specificity. It correctly classified 16 of 22 patients and 22 of 31 controls. Serum from three patients with early-stage pleural malignant mesothelioma, and six plasma samples, did not seem to fall into either group. The authors noted the mesothelioma samples were limited in number. They also acknowledged small sample sizes and no validation in samples from a separate biorepository. They proposed the two microRNAs for future screening and triage use after additional validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case-control biomarker study with a discovery set and a validation set; serum microRNA profiling by microarray followed by quantitative PCR
• Who was studied: Serum from patients with early-stage NSCLC and from healthy controls, nearly all with a tobacco smoking history (one discovery-cohort control had no smoking history). All samples came from the Cancer of RESpiratory Tract biorepository. Discovery cohort: 11 controls and 11 NSCLC patients. Validation cohort: 31 controls and 22 NSCLC patients. Also tested: serum from 3 early-stage mesothelioma patients and 6 plasma samples (4 NSCLC, 2 controls). Most subjects were men.
• Exposure: The article does not report asbestos or fiber exposure. The study measured serum microRNA levels in cancer patients and in controls with a tobacco smoking history.
• Main results:
  • Microarray screening of the discovery cohort covered 880 mature microRNAs. None of the top hits had a false discovery rate less than 0.05. The four mature microRNAs with fold change more than 1.54 were taken forward for PCR testing.
  • Discovery cohort: miR-1254 combined with miR-574-5p best separated early-stage NSCLC from controls, with an area under the curve of 0.77, 82% sensitivity and 77% specificity.
  • Validation cohort: the same pair gave an area under the curve of 0.75, 73% sensitivity and 71% specificity. It correctly classified 16 of 22 NSCLC cases and 22 of 31 controls.
  • The three mesothelioma serum samples and the six plasma samples did not seem to classify into either the NSCLC or the control group.
  • Plasma from 4 NSCLC patients and 2 controls did not consistently classify into either the serum NSCLC group or the serum control group.
• The authors' conclusion: The authors proposed serum miR-1254 and miR-574-5p for future use as minimally invasive screening and triage tools, but only after additional validation in samples collected by other biorepositories.
• Limitations the authors state:
  • The discovery and validation sample sizes were small.
  • The classifier was not validated in samples from a separate, independent biorepository.
  • Only three mesothelioma serum samples were available, and the authors described the mesothelioma results as very preliminary.
  • Two NSCLC samples were collected more than 8 months before diagnosis, but true confirmation of early-stage disease is not available for them.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Biomarker, Non-Small Cell Lung Cancer, Discovery, Mesothelioma.

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