Research Papers:

MiR-21 over-expression and Programmed Cell Death 4 down-regulation features malignant pleural mesothelioma

Lorenzo Nicolè, Rocco Cappellesso, Tiziana Sanavia, Vincenza Guzzardo and Ambrogio Fassina _

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Oncotarget. 2018; 9:17300-17308. https://doi.org/10.18632/oncotarget.24644

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Lorenzo Nicolè1,*, Rocco Cappellesso1,*, Tiziana Sanavia2, Vincenza Guzzardo1 and Ambrogio Fassina1

1Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy

2Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

*These authors have contributed equally to this work

Correspondence to:

Ambrogio Fassina, email: [email protected]

Keywords: PDCD4; miR-21; malignant pleural mesothelioma; immunohistochemistry; prognosis

Received: January 06, 2018     Accepted: February 27, 2018     Published: April 03, 2018


Background: Differential diagnosis between malignant pleural mesothelioma (MPM) and benign mesothelial conditions is still challenging and there is a lack of useful markers. Programmed cell death 4 (PDCD4) is a well-known tumor suppressor gene in several cancers, its post-transcriptional activity is directly controlled by miR-21, whose over-expression has been recently reported in MPM compared to normal mesothelium. Aim of this study was to test this suppressor gene as a possible new marker of malignant transformation in mesothelial cells, as well as a new prognostic marker.

Methods: PDCD4 nuclear expression was assessed by immunohistochemistry (IHC) in 40 non-neoplastic pleural (NNP) and 40 MPM formalin-fixed and paraffin-embedded specimens. PDCD4 and miR-21 expressions were analyzed by qRT-PCR in all cases. In situ hybridization (ISH) of miR-21 was performed in 5 representative cases of both groups. The prognostic relevance of PDCD4 was assessed in a public available gene expression dataset.

Results: IHC showed that PDCD4 nuclear expression was significantly lower in MPM than in NNP. PDCD4 was down-regulated, whereas miR-21 was over-expressed in MPM cases compared to NNP ones. ISH detected miR-21 only in MPM specimens. Down-expression of PDCD4 was found significantly associated with short overall survival in publicly available data.

Conclusions: These findings highlighted a switch between PDCD4 and miR-21 expression in MPM. Further studies should assess the diagnostic reliability of these two markers for MPM in biopsy and effusion specimens.

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