Two Different Serum MiRNA Signatures Correlate with the Clinical Outcome and Histological Subtype in Pleural Malignant Mesothelioma Patients

Our plain-English summary of Two Different Serum MiRNA Signatures Correlate with the Clinical Outcome and Histological Subtype in Pleural Malignant Mesothelioma Patients, by M. Lamberti, R. Capasso, A. Lombardi, et al (PloS One, 2015).

The study

• Authors: M. Lamberti, R. Capasso, A. Lombardi, M. Di Domenico, A. Fiorelli, A. Feola, A.F. Perna, M. Santini, M. Caraglia, D. Ingrosso
• Journal: PloS One
• Published: 2015;10(8):e0135331
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural malignant mesothelioma (MPM) is a detrimental neoplasm affecting pleural sheets and determining a high rate of mortality. In this study, we have enrolled 14 consecutive patients (13 males and 1 female) with MPM (mean age: 70.3 ± 4.6 years). We have collected serum for the determination of a miRNA profiling using a low-density microarray real time PCR system in the serum of patients and comparing it with that one of 10 control counterparts affected by not-cancer-related pleural effusions. In the patients 5 miRNAs were up-regulated (miR101, miR25, miR26b, miR335 and miR433), 2 miRNA were downregulated (miR191, miR223) and two miRNAs were expressed exclusively in patients (miR29a and miR516). Based upon the changes in the expression of the above mentioned miRNAs we detected two distinctive miRNA signatures predicting histotype and survival in these patients: I) patients with more than 3/9 upregulated miRNAs or 3/9 upregulated miRNAs and miR516 not recordable or unchanged (signature A); II) patients with at least 3/9 downregulated or unchanged miRNAs and/or miR29a downregulated (signature B). Based upon these criteria, 5 patients were stratified in signature A and the remaining 9 in signature B. Patients with signature A had a significant shorter median survival than those with signature B (7 months vs. 17 months, 95% CI: 0.098-1.72, p = 0.0021), had a sarcomatoid or mixed histological MPM subtype and were diagnosed in stage II (3/5) and stage III (2/5). In conclusion, we suggest that miRNA signature A is predictive of sarcomatoid histotype and of worse prognosis in MPM.

In plain English

This study, from the Second University of Naples, Italy, measured small RNA molecules called microRNAs (miRNAs) in the blood serum of 14 consecutive patients with pleural malignant mesothelioma (13 men and 1 woman, mean age 70.3 years). It compared them with 10 patients who had fluid around the lungs (pleural effusions) not related to cancer, used as controls. The article does not report anyone's asbestos exposure. Compared with controls, five miRNAs were higher in patients, two were lower, and two (miR29a and miR516) were found only in patients. Based on these miRNAs, the authors sorted the patients into two patterns: signature A (5 patients) and signature B (9 patients). Median survival was 7 months with signature A and 17 months with signature B (95% CI 0.098 to 1.72, p = 0.0021). The methods say survival results were given as hazard ratios with 95% confidence intervals, but no hazard ratio is printed with this interval. All five signature A patients had sarcomatoid or mixed tumors. The authors suggested that signature A predicts the sarcomatoid type and a worse outlook. Several counts in the article do not match its own patient table.

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: Small laboratory biomarker study comparing serum microRNA levels in mesothelioma patients with controls, with a survival analysis (Kaplan-Meier, Cox regression, Gehan-Breslow-Wilcoxon test)
• Who was studied: 14 consecutive patients with pleural malignant mesothelioma (13 males, 1 female; mean age 70.3 years), enrolled at diagnosis at the Division of Chest Surgery, Second University of Naples, Italy. The controls were 10 patients (9 males, 1 female; mean age 68.2 years) with pleural effusions not related to cancer. Enrollment dates are not given; ethics approval was dated 12 January 2014.
• Exposure: Not reported. The article gives no information on asbestos or other exposures of the patients or controls. Asbestos is mentioned only in the introduction, as a general risk factor. The factor studied was serum miRNA levels.
• Main results:
  • Of the subset of 30 miRNAs found in all samples, 5 were higher in patients than in controls (miR101, miR25, miR26b, miR335, miR433), 2 were lower (miR191, miR223), and 2 were found only in patients (miR29a, miR516).
  • Among the 14 patients, tumor types were 3 sarcomatoid, 7 epithelial and 4 mixed. Eight patients were still alive at the time of analysis.
  • 5 patients (all males, mean age 72.8) were classed as signature A, and the remaining 9 as signature B.
  • Median survival was 7 months for signature A patients and 17 months for signature B patients (95% CI 0.098 to 1.72, p = 0.0021). The interval is not labeled in the Results, and no hazard ratio is printed with it. The methods state that survival results were expressed as hazard ratios with 95% confidence intervals.
  • Signature A patients had a sarcomatoid (2/5) or mixed (3/5) tumor type. The article states that all signature A patients had died at the time of analysis.
  • In signature B, 6/9 patients were alive. Tumor types were epithelial (7/9) or mixed (2/9).
  • Stage at diagnosis: signature A patients were stage II (3/5) or stage III (2/5). Signature B patients were stage III (2/9), stage II (2/9) or stage I (5/9).
• The authors' conclusion: The authors suggested that miRNA signature A is predictive of the sarcomatoid tumor type and of a worse prognosis in pleural malignant mesothelioma. They also proposed that patterns of circulating miRNAs may help identify patients with a very poor outcome.

Topics

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

Medical terms in this study, explained in our Lexicon: Histological Subtype, Mesothelioma, Neoplasm, Pleural Effusion, Median Overall Survival, Sarcomatoid, Prognosis.

Related studies

• MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2015)
• MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data — G. Pasello, L. Urso, et al. (2015)
• Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies — L. Santarelli, S. Gaetani, et al. (2019)
• CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis — M. Guled, L. Lahti, et al. (2009)
• Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease — T. Cavalleri, L. Angelici, et al. (2017)
• Serum Expression Levels of Certain miRNAs in Predicting Diagnosis, Prognosis, and Response to Chemotherapy in Malignant Pleural Mesothelioma — M. Metintaş, G. Ak, et al. (2022)

Browse more research in PloS One, or return to medical research.