Putative Drivers for Prognosis in Lung Adenocarcinoma are Race and Gender Specific

Abstract

Lung cancer is the most commonly diagnosed and foremost cause of cancer related mortality. Epidemiological studies have demonstrated significant gender and ethnic differences in trends amongst lung cancer patients. For instance, lung cancers in non-smokers occur disproportionally more frequent amongst East Asian female populations, with most of these cases arising as adenocarcinomas. Meta-analysis of lung adenocarcinomas has been pursued by a number of research groups. However, those studies focus primarily on universal biomarkers common in all datasets, rather than population-specific patterns. This approach gives rise to robust findings, but fails to address the population-specific variations. ??? We identified association modules of genes linking molecular aberrations on DNA with mRNA expressions from integrative datasets (CNVs, DNA methylations, mRNA expressions) of lung adenocarcimas in a never-smoking female Taiwanese cohort. The inferred modules were validated on four datasets from East Asian and Western studies to assess gender and ethnic specificities. Three modules – cis-acting effects with chromosomes 7 and 18 CNVs, and methylations with UBIAD1 and VAV1 – demonstrated strong associations with prognosis amongst the East Asian female subpopulation. Patients possessing high average expression levels in each association module had significantly shorter survival times than patients with low average expression levels. For the module with cis-acting effects on chromosome 18, among other subpopulations (East Asian males, Western males and females) the associations of module members with survival times became insignificant. In contrast, modules with cisacting effects with chromosomes 7 and methylations with UBIAD1 and VAV1 demonstrated an ethnic specificity between East Asians and White Caucasian subpopulations. The study highlights possible module drivers specific to adenocarcinomas amongst East Asian females, and advances the evidence for population specific variation within this histologic sub-type.?