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LINE-1 hypomethylation is associated to specific clinico-pathological features in Stage I non-small cell lung cancer
- Publication Year :
- 2017
- Publisher :
- Elsevier Ireland Ltd, 2017.
-
Abstract
- Objectives We hypothesize that selected genetic and/or epigenetic changes associated with advanced tumours may help identifying early non-small cell lung cancers (NSCLCs) that recur after resection. Among epigenetic changes, long interspersed nuclear element-1 (LINE-1) hypomethylation is seen early during carcinogenesis and may act in concert with genetic alterations to cancer progression. LINE-1 hypomethylation and gene mutations frequently involved in lung cancer, were analysed to evaluate their prognostic role in resected stage I NSCLC. Methods Gene mutations and LINE-1 methylation were analysed in 167 Caucasian patients with stage I NSCLC, namely 100 adenocarcinomas (ADC) and 67 squamous-cell carcinomas (SqCC), using mass-spectrometry and pyrosequencing. We evaluated the correlation between molecular results and clinico-pathological data: age, gender, smoking status, period of surgery, histology, grading, pathological stage, p53 expression, LINE-1 hypomethylation. These variables have been assessed as possible predictors of cancer related survival by regression analysis. Results Frequency and spectrum of gene mutations were significantly different in ADCs compared with SqCCs. p53 positivity was more common in SqCC, while EGFR or KRAS mutations were mainly detected in ADC. LINE1 hypomethylation was associated with SqCC histology, p53 immunoreactivity and smoking habit. Stage IB, LINE-1 hypomethylation and PIK3CA mutation independently predicted a worse cancer-related survival. When combined into a scoring system, their prognostic power was strengthened. Conclusions In many stage I NSCLC a mutation pattern of advanced disease was observed. Stage IB, LINE-1 hypomethylation and PIK3CA mutation were associated to poor prognosis. Genetic and epigenetic events occurring in early carcinogenesis may help identifying stage I NSCLC patients who deserve adjuvant therapy.
- Subjects :
- 0301 basic medicine
Oncology
Male
Pathology
Cancer Research
Lung Neoplasms
DNA Mutational Analysis
Gene mutation
medicine.disease_cause
Epigenesis, Genetic
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
80 and over
Medicine
Non-Small-Cell Lung
Aged, 80 and over
Tumor
Smoking
Middle Aged
Prognosis
030220 oncology & carcinogenesis
Female
KRAS
Lung cancer
Early stage
LINE-1 hypomethylation
Prognostic factors
Surgery
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Aged
Biomarkers, Tumor
Follow-Up Studies
Genetic Association Studies
Humans
Neoplasm Grading
Neoplasm Staging
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Survival Analysis
DNA Methylation
Long Interspersed Nucleotide Elements
03 medical and health sciences
Genetic
Internal medicine
Adjuvant therapy
Matrix-Assisted Laser Desorption-Ionization
Epigenetics
Grading (tumors)
Pathological
business.industry
Spectrometry
Carcinoma
Mass
medicine.disease
030104 developmental biology
business
Carcinogenesis
Biomarkers
Epigenesis
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....572193ed0829d72a7a0c9086152f98d3