Expression level and methylation status of three tumor suppressor genes, DLEC1, ITGA9 and MLH1, in non-small cell lung cancer.
Despite therapeutic advances, lung cancer remains one of the most common causes of cancer-related death in the world. There is a need to develop biomarkers of diagnostic and/or prognostic value and to translate findings in basic science research to clinical application. Tumor suppressor genes (TSGs) represent potential useful markers for disease detection, progression and treatment target. We tried to elucidate the role of three 3p21.3 TSGs: DLEC1, ITGA9 and MLH1, in non-small cell lung cancer (NSCLC). We assessed their expression pattern by qPCR in 59 NSCLC tissues and in the matched macroscopically unchanged lung tissues. Additionally, we analyzed gene promoter methylation status by methylation-specific PCR in NSCLC samples. We did not find significant correlations between gene expression and methylation. In case of DLEC1 and ITGA9, expression levels were decreased in 71-78 % of tumor samples and significantly different between tumor and normal tissues (P = 0.0001). It could point to their diagnostic value. ITGA9 could also be regarded as a diagnostic marker differentiating NSCLC subtypes, as its expression level was significantly lower in squamous cell carcinoma (P = 0.001). The simultaneous down-regulation of DLEC1 and ITGA9 was observed in 52.5 % of NSCLCs. MSPs revealed high frequencies of gene promoter methylation in NSCLCs: 84 % for DLEC1 and MLH1 and 57 % for ITGA9. Methylation indexes reflected moderate gene methylation levels: 34 % for ITGA9, 27 % for MLH1 and 26 % for DLEC1. However, frequent simultaneous methylation of the studied genes in more than 50 % of NSCLCs suggests the possibility of consider them as a panel of epigenetic markers.
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. no. 251, C5, 92-213, Lodz, Poland. dorota.pastuszak-lewandoska@umed.lodz.pl.
Dorota
http://orcid.org/0000-0001-7602-9203
D
Pastuszak-Lewandoska
Department of Chest Surgery, General and Oncological Surgery, University Hospital No. 2, Medical University of Lodz, Lodz, Poland.
Jacek
J
Kordiak
Department of General and Oncological Pulmonology, Medical University of Lodz, Lodz, Poland.
Adam
A
Antczak
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. no. 251, C5, 92-213, Lodz, Poland.
Monika
M
Migdalska-Sęk
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. no. 251, C5, 92-213, Lodz, Poland.
Karolina H
KH
Czarnecka
Department of Pneumology and Allergology, Medical University of Lodz, Lodz, Poland.
Paweł
P
Górski
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. no. 251, C5, 92-213, Lodz, Poland.
Ewa
E
Nawrot
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. no. 251, C5, 92-213, Lodz, Poland.
Justyna M
JM
Kiszałkiewicz
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. no. 251, C5, 92-213, Lodz, Poland.
Daria
D
Domańska-Senderowska
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. no. 251, C5, 92-213, Lodz, Poland.
Ewa
E
Brzeziańska-Lasota
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D016023:Integrins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C119064:DLEC1 protein, human; C541973:ITGA9 protein, human; D016023:Integrins; C501486:MLH1 protein, human; D025521:Tumor Suppressor Proteins; D000070957:MutL Protein Homolog 1
Biomarker; Gene expression; Non-small cell lung cancer; Promoter methylation; Tumor suppressor gene