Systems biology analysis of publicly available transcriptomic data reveals a critical link between AKR1B10 gene expression, smoking and occurrence of lung cancer

AbstractBackgroundCigarette smoking is associated with increased risk of developing respiratory diseases and various types of cancer. Early identification of such unfavorable outcomes in patients who smoke is critical for optimizing personalized medical care.MethodsHere, we perform a comprehensive analysis using Systems Biology tools of publicly available data from a total of six transcriptomic studies, which examined different specimens of lung tissue and/or cells of smokers and nonsmokers to identify potential markers associated with lung cancer.ResultsExpression level of twenty-two genes was capable of classifying smokers from non-smokers. A machine learning algorithm revealed that AKR1B10 was the most informative gene among the 22 DEGs accounting for the classification of the clinical groups. AKR1B10 expression was higher in smokers compared to non-smokers in datasets examining small and large airway epithelia, but not in the data from a study of sorted alveolar macrophages. We next tested whether AKR1B10 expression could be useful in identification of cancer tissue in patients who were not exposed to smoking. AKR1B10 expression was substantially higher in lung cancer specimens compared to matched healthy tissue obtained from nonsmoking individuals (accuracy: 80%, p<0.0001). Finally, we searched the expression of 11 single nucleotide polymorphisms (SNPs) of AKR1B10 worldwide. We found that the SNP rs782881 was the most frequent mutant allele in the majority of continents. Africa was the continent which exhibited higher frequency of SNPs associated with lower AKR1B10 expression and displayed lower lung cancer incidence and deaths attributable to tobacco.ConclusionThe systematic analysis of transcriptomic studies performed here revealed a potential critical link between AKR1B10 expression, smoking and occurrence of lung cancer.