If scientists and researchers understood the molecular mechanisms of tumorigenesis, lung cancer could be eradicated. A recent study made one more step forward in the goal of understanding lung cancer by studying the reproducibility of differentially expressed genes in the case of non-smoking women with lung adenocarcinomas.
“Although countless research efforts have been devoted to understanding the etiology of lung cancer, the tumorigenesis process still remains unclear,” wrote study author Dr. Tzu-Pin Lu in the Department of Public Health, Institute of Epidemiology and Preventive Medicine at National Taiwan University. “Consequently, even if many prognostic biomarkers have been identified for predicting survival outcomes for lung cancer patients, their application is usually limited due to the low reproducibility. Thus, an integrated analysis of gene expression and methylation alterations may help to improve the understanding of gene regulation mechanisms in lung cancer.”
To conduct the study, “Identification of Regulatory SNPs Associated with Genetic Modifications in Lung Adenocarcinoma,” which was published in BMC Research Notes, Dr. Lu and his fellow researchers looked at copy number variations (CNVs) and methylation alterations in 32 female lung cancer patients who had never smoked. Both CNVs and methylation alterations are modifications to genes and can be analyzed to increase reproducibility of prognostic biomarkers.
The team used gene expression analysis on two tissue samples from each patient and assessed the number and type of single nucleotide polymorphisms (SNPs), gene methylation profiles, and CNVs. One tissue sample was cancerous and the other sample was from adjacent healthy tissue. After analyses, the team identified 505 genes with significantly different expression between the two tissue types. Of these genes, 369 were under-produced and 136 were over-produced in cancerous tissue.
Such a stark contrast prompted the question of why genes were dysregulated in tumorogenic tissue. This is where CNV analysis and whole genome methylation profiles came into play. Methylation alterations were closely related to down-regulated gene expression, but CNVs were variable in the direction of agreement. “Gene expression analysis further demonstrated that several SNP alleles with genetic modifications correlated with downstream transcriptional changes,” stated Dr. Lu.
Using these data as a starting point, future studies will be able to investigate further the connection between SNPs and lung cancer.
