TY - JOUR
T1 - Promoter Methylation of Selected Genes in Non-Small-Cell Lung Cancer Patients and Cell Lines
AU - Sarne, Victoria
AU - Huter, Samuel
AU - Braunmueller, Sandrina
AU - Rakob, Lisa
AU - Jacobi, Nico
AU - Kitzwögerer, Melitta
AU - Wiesner, Christoph
AU - Obrist, Peter
AU - Seeboeck, Rita
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/7
Y1 - 2020/7
N2 - Specific gene promoter DNA methylation is becoming a powerful epigenetic biomarker in cancer diagnostics. Five genes (CDH1, CDKN2Ap16, RASSF1A, TERT, and WT1) were selected based on their frequently published potential as epigenetic markers. Diagnostic promoter methylation assays were generated based on bisulfite-converted DNA pyrosequencing. The methylation patterns of 144 non-small-cell lung cancer (NSCLC) and 7 healthy control formalin-fixed paraffin-embedded (FFPE) samples were analyzed to evaluate the applicability of the putative diagnostic markers. Statistically significant changes in methylation levels are shown for TERT and WT1. Furthermore, 12 NSCLC and two benign lung cell lines were characterized for promoter methylation. The in vitro tests involved a comparison of promoter methylation in 2D and 3D cultures, as well as therapeutic tests investigating the impact of CDH1/CDKN2Ap16/RASSF1A/TERT/WT1 promoter methylation on sensitivity to tyrosine kinase inhibitor (TKI) and DNA methyl-transferase inhibitor (DNMTI) treatments. We conclude that the selected markers have potential and putative impacts as diagnostic or even predictive marker genes, although a closer examination of the resulting protein expression and pathway regulation is needed.
AB - Specific gene promoter DNA methylation is becoming a powerful epigenetic biomarker in cancer diagnostics. Five genes (CDH1, CDKN2Ap16, RASSF1A, TERT, and WT1) were selected based on their frequently published potential as epigenetic markers. Diagnostic promoter methylation assays were generated based on bisulfite-converted DNA pyrosequencing. The methylation patterns of 144 non-small-cell lung cancer (NSCLC) and 7 healthy control formalin-fixed paraffin-embedded (FFPE) samples were analyzed to evaluate the applicability of the putative diagnostic markers. Statistically significant changes in methylation levels are shown for TERT and WT1. Furthermore, 12 NSCLC and two benign lung cell lines were characterized for promoter methylation. The in vitro tests involved a comparison of promoter methylation in 2D and 3D cultures, as well as therapeutic tests investigating the impact of CDH1/CDKN2Ap16/RASSF1A/TERT/WT1 promoter methylation on sensitivity to tyrosine kinase inhibitor (TKI) and DNA methyl-transferase inhibitor (DNMTI) treatments. We conclude that the selected markers have potential and putative impacts as diagnostic or even predictive marker genes, although a closer examination of the resulting protein expression and pathway regulation is needed.
KW - Aged
KW - Antigens, CD/genetics
KW - Biomarkers, Tumor/genetics
KW - Cadherins/genetics
KW - Carcinoma, Non-Small-Cell Lung/genetics
KW - DNA Methylation
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Lung Neoplasms/genetics
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Promoter Regions, Genetic
KW - Tumor Cells, Cultured
UR - http://www.scopus.com/inward/record.url?scp=85087289391&partnerID=8YFLogxK
U2 - 10.3390/ijms21134595
DO - 10.3390/ijms21134595
M3 - Journal article
C2 - 32605217
SN - 1661-6596
VL - 21
SP - 1
EP - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 13
M1 - 4595
ER -