Identification of circulating miRNAs profiles that distinguish malignant pleural mesothelioma from lung adenocarcinoma

Our plain-English summary of Identification of circulating miRNAs profiles that distinguish malignant pleural mesothelioma from lung adenocarcinoma, by L.V. Gayosso-Gómez, G. Zárraga-Granados, P. Paredes-Garcia, et al (EXCLI Journal, 2014).

The study

• Authors: L.V. Gayosso-Gómez, G. Zárraga-Granados, P. Paredes-Garcia, R. Falfán-Valencia, M.E. Vazquez-Manríquez, L.M. Martinez-Barrera, P. Castillo-Gonzalez, U. Rumbo-Nava, R. Guevara-Gutierrez, B. Rivera-Bravo, A. Ramirez-Venegas, R. Sansores, M.C. Negrete-Garcia, B. Ortiz-Quintero
• Journal: EXCLI Journal
• Published: 2014;13:740-50
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed.

In plain English

This laboratory study looked for blood molecules called microRNAs (miRNAs) that might help tell malignant pleural mesothelioma (MPM) apart from lung adenocarcinoma (AD). Both diseases were diagnosed from tissue. Patients with epithelioid MPM (11) and AD (36: 15 non-smokers, 21 smokers) came from a respiratory hospital in Mexico City. Forty-five healthy smokers were recruited separately as controls through an anti-smoking and blood donation campaign there. Serum was pooled into five combined samples (one MPM, two AD, two control) and analyzed by deep sequencing. About 300 known miRNAs were detected. Compared with healthy controls, 7 known miRNAs were higher in the MPM pool and 12 in the AD pools. Three were unique to MPM. Comparing MPM directly with AD, 13 miRNAs were higher and 5 lower in MPM. Two miRNAs, hsa-miR-1292-5p and hsa-miR-409-5p, were higher in MPM in both comparisons. The article does not mention asbestos. The authors concluded that serum miRNA profiles may be a suitable non-invasive tool for distinguishing MPM from AD. They said their results need to be checked with a quantitative method and in individual serum samples.

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: Laboratory biomarker screening study using deep sequencing of pooled serum samples. There were five pools: one MPM, two AD (non-smokers and smokers) and two control (men and women).
• Who was studied: Participants were over 35 years old and came from the Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City. There were 11 patients with epithelioid MPM (10 men and 1 woman; 9 smokers) and 36 patients with lung adenocarcinoma (15 non-smokers and 21 smokers). The 45 healthy smoker controls (23 men and 22 women) were recruited separately through an anti-smoking and blood donation campaign at the same institute. No study dates are given.
• Exposure: The study did not assess asbestos and does not mention it. It compared serum miRNA levels between disease groups. Smoking and wood smoke exposure were recorded: in the MPM group, 9 of 11 were smokers and 4 had wood smoke exposure.
• Main results:
  • Sequencing detected about 300 unique known miRNAs and up to 25 novel miRNAs across the serum pools.
  • Compared with healthy controls, 7 known miRNAs were upregulated in the MPM serum pool and 12 in the AD serum pools.
  • No novel miRNAs differed between either cancer group and the controls.
  • Four of the upregulated miRNAs were shared by MPM and AD. Three were unique to MPM (hsa-miR-1292-5p, hsa-miR-409-5p and hsa-miR-92b-5p), and eight were unique to AD.
  • In a direct comparison of MPM with AD, 13 miRNAs were upregulated and 5 were downregulated in MPM.
  • hsa-miR-1292-5p and hsa-miR-409-5p were upregulated in MPM both compared with AD and compared with healthy controls.
  • A computer analysis predicted 1,115 target genes for the seven miRNAs upregulated in MPM. The p38 MAPK signaling pathway was the top enriched pathway (raw p = 3.04E-03). Three of these miRNAs (hsa-miR-96-5p, hsa-miR-1271 and hsa-miR-409-5p) were predicted to target genes in p38-related pathways.
• The authors' conclusion: The authors concluded that serum miRNA profiles may be a suitable non-invasive tool for distinguishing MPM from AD. They pointed to several miRNAs as potential diagnostic biomarkers for MPM.
• Limitations the authors state:
  • The results have not been confirmed by a quantitative method such as real-time polymerase chain reaction.
  • Only pooled serum was tested; the results need to be checked in individual serum samples.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Lung Adenocarcinoma, Pleura, Mesothelioma, Differential Diagnosis, Biomarker.

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