KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer
MLL3 histone methyltransferase, encoded by the KMT2C gene, is a tumor suppressor that has an essential role in cell‐type‐specific gene expression. We evaluated the prognostic significance of KMT2C promoter methylation as a circulating epigenetic biomarker in plasma cell‐free DNA (cfDNA) in non‐small...
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doaj-ac1d7c9c14a84789a0789d2ca92edcf42021-09-02T02:01:46ZengWileyMolecular Oncology1574-78911878-02612021-09-011592412242210.1002/1878-0261.12848KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancerSofia Mastoraki0Ioanna Balgkouranidou1Emily Tsaroucha2Apostolos Klinakis3Vassilis Georgoulias4Evi Lianidou5Analysis of Circulating Tumor Cells Lab of Analytical Chemistry Department of Chemistry University of Athens GreeceAnalysis of Circulating Tumor Cells Lab of Analytical Chemistry Department of Chemistry University of Athens Greece8th Department of Pulmonary Diseases ‘Sotiria’ General Hospital for Chest Diseases Athens GreeceBiomedical Research Foundation Academy of Athens GreeceDepartment of Medical Oncology IASO General Hospital Athens GreeceAnalysis of Circulating Tumor Cells Lab of Analytical Chemistry Department of Chemistry University of Athens GreeceMLL3 histone methyltransferase, encoded by the KMT2C gene, is a tumor suppressor that has an essential role in cell‐type‐specific gene expression. We evaluated the prognostic significance of KMT2C promoter methylation as a circulating epigenetic biomarker in plasma cell‐free DNA (cfDNA) in non‐small cell lung cancer (NSCLC). We examined the methylation status of KMT2C promoter using a novel highly specific and sensitive real‐time methylation‐specific PCR (MSP) assay in (a) operable NSCLC: 48 fresh‐frozen NSCLC tissues, their corresponding adjacent non‐neoplastic tissues, and 48 matched plasma samples; (b) metastatic NSCLC: 91 plasma samples; and (c) 60 plasma samples from healthy donors (HD). KMT2C promoter methylation in plasma cfDNA was detected in 7/48 (14.6%) patients with operable and in 18/91 (19.8%) patients with advanced NSCLC but in none (0/60, 0%) of the plasma samples from HD. In operable NSCLC, in corresponding adjacent non‐neoplastic tissue samples, KMT2C promoter methylation was detected in 3/48 (6.3%) cases. Moreover, in operable NSCLC, KMT2C promoter methylation in plasma cfDNA was related to reduced disease‐free survival (ΗR = 0.239; P = 0.001) and worse overall survival (OS; HR = 0.342, P = 0.023). In metastatic NSCLC, KMT2C promoter methylation in plasma cfDNA was related to worse progression‐free survival (PFS; HR = 0.431; P = 0.005) and worse OS (HR = 0.306; P < 0.001). Our data strongly suggest that the detection of KMT2C promoter methylation in plasma cfDNA predicts poor prognosis in patients with both operable and metastatic NSCLCs. KMT2C promoter methylation in plasma cfDNA therefore merits further evaluation and validation as a noninvasive circulating epigenetic biomarker.https://doi.org/10.1002/1878-0261.12848cfDNAepigenetic biomarkersKMT2Cliquid biopsyMLL3NSCLC |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sofia Mastoraki Ioanna Balgkouranidou Emily Tsaroucha Apostolos Klinakis Vassilis Georgoulias Evi Lianidou |
spellingShingle |
Sofia Mastoraki Ioanna Balgkouranidou Emily Tsaroucha Apostolos Klinakis Vassilis Georgoulias Evi Lianidou KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer Molecular Oncology cfDNA epigenetic biomarkers KMT2C liquid biopsy MLL3 NSCLC |
author_facet |
Sofia Mastoraki Ioanna Balgkouranidou Emily Tsaroucha Apostolos Klinakis Vassilis Georgoulias Evi Lianidou |
author_sort |
Sofia Mastoraki |
title |
KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer |
title_short |
KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer |
title_full |
KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer |
title_fullStr |
KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer |
title_full_unstemmed |
KMT2C promoter methylation in plasma‐circulating tumor DNA is a prognostic biomarker in non‐small cell lung cancer |
title_sort |
kmt2c promoter methylation in plasma‐circulating tumor dna is a prognostic biomarker in non‐small cell lung cancer |
publisher |
Wiley |
series |
Molecular Oncology |
issn |
1574-7891 1878-0261 |
publishDate |
2021-09-01 |
description |
MLL3 histone methyltransferase, encoded by the KMT2C gene, is a tumor suppressor that has an essential role in cell‐type‐specific gene expression. We evaluated the prognostic significance of KMT2C promoter methylation as a circulating epigenetic biomarker in plasma cell‐free DNA (cfDNA) in non‐small cell lung cancer (NSCLC). We examined the methylation status of KMT2C promoter using a novel highly specific and sensitive real‐time methylation‐specific PCR (MSP) assay in (a) operable NSCLC: 48 fresh‐frozen NSCLC tissues, their corresponding adjacent non‐neoplastic tissues, and 48 matched plasma samples; (b) metastatic NSCLC: 91 plasma samples; and (c) 60 plasma samples from healthy donors (HD). KMT2C promoter methylation in plasma cfDNA was detected in 7/48 (14.6%) patients with operable and in 18/91 (19.8%) patients with advanced NSCLC but in none (0/60, 0%) of the plasma samples from HD. In operable NSCLC, in corresponding adjacent non‐neoplastic tissue samples, KMT2C promoter methylation was detected in 3/48 (6.3%) cases. Moreover, in operable NSCLC, KMT2C promoter methylation in plasma cfDNA was related to reduced disease‐free survival (ΗR = 0.239; P = 0.001) and worse overall survival (OS; HR = 0.342, P = 0.023). In metastatic NSCLC, KMT2C promoter methylation in plasma cfDNA was related to worse progression‐free survival (PFS; HR = 0.431; P = 0.005) and worse OS (HR = 0.306; P < 0.001). Our data strongly suggest that the detection of KMT2C promoter methylation in plasma cfDNA predicts poor prognosis in patients with both operable and metastatic NSCLCs. KMT2C promoter methylation in plasma cfDNA therefore merits further evaluation and validation as a noninvasive circulating epigenetic biomarker. |
topic |
cfDNA epigenetic biomarkers KMT2C liquid biopsy MLL3 NSCLC |
url |
https://doi.org/10.1002/1878-0261.12848 |
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