Cargando…

Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer

The silencing of SPARC (secreted protein acid and rich in cysteine) gene through methylation of its promoter region represents a common event in many solid tumors and it is frequently associated with tumor progression and an aggressive clinical outcome. Anyhow, the data concerning the epigenetic mec...

Descripción completa

Detalles Bibliográficos
Autores principales: Fabrizio, Federico Pio, Sparaneo, Angelo, Fontana, Andrea, Mazza, Tommaso, Graziano, Paolo, Pantalone, Angela, Parente, Paola, Centra, Flavia, Orlando, Natalizia, Trombetta, Domenico, la Torre, Annamaria, Ferretti, Gian Maria, Taurchini, Marco, Di Micco, Concetta Martina, Maiello, Evaristo, Fazio, Vito Michele, Rossi, Antonio, Muscarella, Lucia Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349117/
https://www.ncbi.nlm.nih.gov/pubmed/32580473
http://dx.doi.org/10.3390/cells9061523
_version_ 1783556988700983296
author Fabrizio, Federico Pio
Sparaneo, Angelo
Fontana, Andrea
Mazza, Tommaso
Graziano, Paolo
Pantalone, Angela
Parente, Paola
Centra, Flavia
Orlando, Natalizia
Trombetta, Domenico
la Torre, Annamaria
Ferretti, Gian Maria
Taurchini, Marco
Di Micco, Concetta Martina
Maiello, Evaristo
Fazio, Vito Michele
Rossi, Antonio
Muscarella, Lucia Anna
author_facet Fabrizio, Federico Pio
Sparaneo, Angelo
Fontana, Andrea
Mazza, Tommaso
Graziano, Paolo
Pantalone, Angela
Parente, Paola
Centra, Flavia
Orlando, Natalizia
Trombetta, Domenico
la Torre, Annamaria
Ferretti, Gian Maria
Taurchini, Marco
Di Micco, Concetta Martina
Maiello, Evaristo
Fazio, Vito Michele
Rossi, Antonio
Muscarella, Lucia Anna
author_sort Fabrizio, Federico Pio
collection PubMed
description The silencing of SPARC (secreted protein acid and rich in cysteine) gene through methylation of its promoter region represents a common event in many solid tumors and it is frequently associated with tumor progression and an aggressive clinical outcome. Anyhow, the data concerning the epigenetic mechanism of SPARC deregulation and its prognostic value in lung cancer are still incomplete. We explored the aberrant methylation of SPARC and its effects in 4 non-small cell lung cancer (NSCLC) cell lines and 59 NSCLC tissues and correlated the methylation levels with clinical-pathological features and disease outcome of patients. In 3 out of 4 tumor cell lines high SPARC methylation levels were observed. An inverse correlation between the epigenetic silencing and SPARC expression was confirmed by 5-Aza-2′-deoxycytidine ((5-Aza-CdR) treatment that also significantly induced a reduction in cell viability, proliferation and tumor cell migration. In tissues, the DNA methylation levels of the SPARC gene were significantly lower in paired non-neoplastic lungs (NLs) and normal lungs distant from tumor (NLDTs) than in NSCLCs (p = 0.002 and p = 0.0034 respectively). A promoter hypermethylation was detected in 68% of squamous cell carcinoma (SqCCs, 17/25) and 56% of adenocarcinoma (ADCs, 19/34), with SqCC showing the highest levels of methylation. Higher SPARC methylation levels were significantly associated with higher mortality risk both in all NSCLCs early stage patients (Hazard Ratio, HR = 1.97; 95% Confidence Interval, CI: 1.32–2.93; p = 0.001) and in those with SqCC (HR = 2.96; 95% CI: 1.43–6.12; p = 0.003). Promoter methylation of SPARC gene should represent an interesting prognostic biomarker in NSCLC, with potential application in the squamous early-stage context. Further research in this setting on larger independent cohorts of lung patients with different histologies and stages of disease are warranted.
format Online
Article
Text
id pubmed-7349117
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-73491172020-07-22 Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer Fabrizio, Federico Pio Sparaneo, Angelo Fontana, Andrea Mazza, Tommaso Graziano, Paolo Pantalone, Angela Parente, Paola Centra, Flavia Orlando, Natalizia Trombetta, Domenico la Torre, Annamaria Ferretti, Gian Maria Taurchini, Marco Di Micco, Concetta Martina Maiello, Evaristo Fazio, Vito Michele Rossi, Antonio Muscarella, Lucia Anna Cells Article The silencing of SPARC (secreted protein acid and rich in cysteine) gene through methylation of its promoter region represents a common event in many solid tumors and it is frequently associated with tumor progression and an aggressive clinical outcome. Anyhow, the data concerning the epigenetic mechanism of SPARC deregulation and its prognostic value in lung cancer are still incomplete. We explored the aberrant methylation of SPARC and its effects in 4 non-small cell lung cancer (NSCLC) cell lines and 59 NSCLC tissues and correlated the methylation levels with clinical-pathological features and disease outcome of patients. In 3 out of 4 tumor cell lines high SPARC methylation levels were observed. An inverse correlation between the epigenetic silencing and SPARC expression was confirmed by 5-Aza-2′-deoxycytidine ((5-Aza-CdR) treatment that also significantly induced a reduction in cell viability, proliferation and tumor cell migration. In tissues, the DNA methylation levels of the SPARC gene were significantly lower in paired non-neoplastic lungs (NLs) and normal lungs distant from tumor (NLDTs) than in NSCLCs (p = 0.002 and p = 0.0034 respectively). A promoter hypermethylation was detected in 68% of squamous cell carcinoma (SqCCs, 17/25) and 56% of adenocarcinoma (ADCs, 19/34), with SqCC showing the highest levels of methylation. Higher SPARC methylation levels were significantly associated with higher mortality risk both in all NSCLCs early stage patients (Hazard Ratio, HR = 1.97; 95% Confidence Interval, CI: 1.32–2.93; p = 0.001) and in those with SqCC (HR = 2.96; 95% CI: 1.43–6.12; p = 0.003). Promoter methylation of SPARC gene should represent an interesting prognostic biomarker in NSCLC, with potential application in the squamous early-stage context. Further research in this setting on larger independent cohorts of lung patients with different histologies and stages of disease are warranted. MDPI 2020-06-22 /pmc/articles/PMC7349117/ /pubmed/32580473 http://dx.doi.org/10.3390/cells9061523 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fabrizio, Federico Pio
Sparaneo, Angelo
Fontana, Andrea
Mazza, Tommaso
Graziano, Paolo
Pantalone, Angela
Parente, Paola
Centra, Flavia
Orlando, Natalizia
Trombetta, Domenico
la Torre, Annamaria
Ferretti, Gian Maria
Taurchini, Marco
Di Micco, Concetta Martina
Maiello, Evaristo
Fazio, Vito Michele
Rossi, Antonio
Muscarella, Lucia Anna
Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer
title Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer
title_full Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer
title_fullStr Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer
title_full_unstemmed Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer
title_short Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer
title_sort potential prognostic role of sparc methylation in non-small-cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349117/
https://www.ncbi.nlm.nih.gov/pubmed/32580473
http://dx.doi.org/10.3390/cells9061523
work_keys_str_mv AT fabriziofedericopio potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT sparaneoangelo potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT fontanaandrea potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT mazzatommaso potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT grazianopaolo potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT pantaloneangela potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT parentepaola potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT centraflavia potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT orlandonatalizia potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT trombettadomenico potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT latorreannamaria potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT ferrettigianmaria potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT taurchinimarco potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT dimiccoconcettamartina potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT maielloevaristo potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT faziovitomichele potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT rossiantonio potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer
AT muscarellaluciaanna potentialprognosticroleofsparcmethylationinnonsmallcelllungcancer