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

Autor: Fabrizio FP; Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Sparaneo A; Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Fontana A; Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Mazza T; Unit of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Graziano P; Unit of Pathology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Pantalone A; Department of Medicine, R.U. in Molecular Medicine and Biotechnology, University Campus Bio-Medico of Rome, 00128 Rome, Italy., Parente P; Unit of Pathology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Centra F; Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Orlando N; Unit of Pathology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Trombetta D; Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Torre A; Advanced Therapies Production Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Ferretti GM; Thoracic-Surgery Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Taurchini M; Thoracic-Surgery Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Micco CMD; Medical Oncology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Maiello E; Medical Oncology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Fazio VM; Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy.; Department of Medicine, R.U. in Molecular Medicine and Biotechnology, University Campus Bio-Medico of Rome, 00128 Rome, Italy., Rossi A; Medical Oncology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy., Muscarella LA; Laboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy.
Jazyk: angličtina
Zdroj: Cells [Cells] 2020 Jun 22; Vol. 9 (6). Date of Electronic Publication: 2020 Jun 22.
DOI: 10.3390/cells9061523
Abstrakt: 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.
Databáze: MEDLINE
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