Two Different Serum MiRNA Signatures Correlate with the Clinical Outcome and Histological Subtype in Pleural Malignant Mesothelioma Patients.
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.
Department of Experimental Medicine, Section of Hygiene, Occupational Medicine and Forensic Medicine, School of Medicine, Second University of Naples, Naples, Italy.
Monica
M
Lamberti
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy.
Rosanna
R
Capasso
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy.
Angela
A
Lombardi
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy.
Marina
M
Di Domenico
Department of Thoracic Surgery, School of Medicine, Second University of Naples, Naples, Italy.
Alfonso
A
Fiorelli
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy.
Antonia
A
Feola
Department of Cardiothoracic & Respiratory Sciences, Second University of Naples, Naples, Italy.
Alessandra F
AF
Perna
Department of Thoracic Surgery, School of Medicine, Second University of Naples, Naples, Italy.
Mario
M
Santini
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy.
Michele
M
Caraglia
Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy.
Diego
D
Ingrosso
D000368:Aged; D014408:Biomarkers, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis
D014408:Biomarkers, Tumor; D035683:MicroRNAs