Identification of genes and pathways associated with sex in Non-smoking lung cancer population
Identification of genes and pathways associated with sex in Non-smoking lung cancer population
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非吸烟肺癌人群中与性别相关的基因和通路的鉴定
DOI：
10.1016/j.gene.2022.146566
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发表时间：
2022-05-18
期刊：
影响因子：
3.5
通讯作者：
Cheng, Minzhang
中科院分区：
文献类型：
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作者：
Xu, Linlin;Wang, Lingchen;Cheng, Minzhang
导言：与吸烟者相比，在非吸烟者中，女性肺癌患者的比例高于男性。这一比例异常高的原因尚不清楚，但性别差异表明可能有遗传因素在起作用。材料和方法：通过Illumina RNA测序确定肺癌患者的基因表达，并从TCGA下载相关的临床资料。在不吸烟和吸烟人群中筛选了男性和女性之间的差异表达基因(Deg)。前50个经过验证的DEG用热图表示。在此基础上，进行了GO功能和KEGG途径的富集性分析。构建了PPI网络，以进一步说明部门之间的直接和间接关联。采用生存分析的方法探讨这些基因对肺癌患者预后的影响。结果：在非吸烟患者中，女性明显多于男性(女性73.0%，男性27.0%，P<；0.001)。在吸烟者中无此差异(女性50.7%，男性49.3%，P=0.770)。在不吸烟的人群中总共发现了898个DEG，而在吸烟的人群中总共发现了992个DEG。在这些基因中，只有122个基因是两个群体共有的。在非吸烟人群中，cAMP信号转导通路、卵巢类固醇激素生成等信号转导途径发生了特异性的丰富。与雌激素功能和MAPK/PI3K信号相关的几个蛋白，如KRT16、ERBB4和NTF4，在不吸烟的男性和女性的肺腺癌进展中显示出不同的作用。结论：在非吸烟肺腺癌患者中，男性和女性之间存在一定的遗传差异。ER信号和MAPK/PI3K信号可能部分参与了这种差异。
Introduction: 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. Materials and Methods: 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. Results: In non-smoking patients, there were significantly more females than males (female 73.0% vs male 27.0%, P < 0.001). Such difference was not found in smoking patients (female 50.7% vs male 49.3%, P = 0.770). A total of 898 DEGs were identified in the non-smoking population, while a total of 992 DEGs were identified in the smoking population. Of these, only 122 genes were shared by both populations. Some pathways were enriched specifical in non-smoking population, such as cAMP signaling pathway and ovarian steroidogenesis. 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. Conclusions: Some genetic differences between male and female in non-smoking lung adenocarcinoma patients have been identified. Potentially, ER signaling and MAPK/PI3K signaling partially participated in this discrepancy.