1559P - A novel prognostic microRNA signature in malignant pleural mesothelioma

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Mesothelioma
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Francesco Grossi
Citation Annals of Oncology (2014) 25 (suppl_4): iv542-iv545. 10.1093/annonc/mdu357
Authors F. Grossi1, A. Truini1, E. Nadal2, C. Genova1, E. Rijavec1, G. Barletta1, F. Biello1, D.G. Beer2, S. Coco1
  • 1Lung Cancer Unit, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT
  • 2Department Of Surgery, University of Michigan, Ann Arbor/US

Abstract

Aim

Malignant pleural mesothelioma (MPM) is an aggressive tumor predominantly associated with asbestos exposure. The prognosis is particularly severe and novel approaches are needed. MicroRNA (miR) play a role in tumorigenesis in MPM. The aim of this study was to identify miR associated with poor prognosis in MPM which may be potentially actionable targets.

Methods

We identified 11 long survivors (LS,>36 months) and 15 short survivors (SS,<12 months) diagnosed at the IRCCS AOU San Martino-IST (Genova) from 1998-2008 that did not undergo tumor resection. Sections from FFPE biopsy blocks were macrodissected and RNA was extracted. Twenty-six MPM and 3 additional normal pleura (NP) were miR profiled using the Agilent platform Human miRNA Microarray 8x60K including 2006 miR. Expression data were normalized using GeneSpring software (v.12.6). Class-comparison analysis between MPM/NP and SS/LS was performed using a t-test adjusted for multiple comparisons using Benjamini-Hochberg. Overall survival (OS) curves were estimated using the Kaplan-Meier method and compared with the log-rank test.

Results

Patients' characteristics: median age, 67 years; males (81%), females (19%). The most frequent histotype was epithelioid (69%), followed by sarcomatoid (12%), biphasic (4%) and 15% unknown. No differences in age, gender and histotype were observed among LS and SS. By class-comparison analysis, 30 miR were significantly up-regulated and 11 down-regulated in MPM versus NP (adjusted p-value <0.05). The univariate survival analysis showed 14 miR significantly associated with outcome and differentially expressed in MPM. A miR signature was calculated based on the top 5 prognostic miR (miR-1224,-99a, let-7b, let-7c, let-7i) and patients were classified into low or high-risk. High-risk patients had a significantly shorter median OS (4.1 months, 95% CI 2.2-5.9) as compared with low-risk (median not reached, Log-rank p<0.001). Relevant pathways, such as PI3K/AKT, WNT, p53 and MAPK, were associated with these top 5 miR by pathway analysis based on predicted targeted genes.

Conclusions

A prognostic miR signature was identified by profiling a cohort of unresected MPM. Further validation is warranted using an independent cohort of MPM.

Disclosure

All authors have declared no conflicts of interest.