Identification of genes and pathways associated with sex in Non-smoking lung cancer population

•Different expression genes between males and females in both non-smoking or smoking lung adenocarcinoma patients have been identified.•Multiple signaling pathways, such as ER signaling and MAPK/PI3K signaling potentially participated in genetic differences between male and female in non-smoking lung adenocarcinoma patients.•Several proteins related to estrogen function and MAPK/PI3K signaling, such as KRT16, ERBB4 and NTF4, showed differential effects on the lung adenocarcinoma progression in non-smoking males or females. Women represent a higher proportion than men among those with lung cancer in nonsmokers compared to smokers. The reason for this abnormally higher proportion is not yet clear, but sex differences suggest there may be a genetic component at play. The gene expression determined by Illumina RNA Sequencing and the relevant clinical information of lung cancer patients was download from TCGA. The differentially expressed genes (DEGs) were screened between males and females in both nonsmoking and smoking populations. The top 50 validated DEGs are represented with heatmaps. Based on the DEGs, GO functional and KEGG pathway enrichment analyses were performed. PPI networks were constructed to further illustrate the direct and indirect associations among the DEGs. Survival analysis was performed to explore whether these genes can affect lung cancer patient prognosis. In non-smoking patients, there were significantly more females than males (female 73.0% vs male 27.0%, P