Araujo Jhajaira M, Prado Alexandra, Cardenas Nadezhda K, Zaharia Mayer, Dyer Richard, Doimi Franco, Bravo Leny, Pinillos Luis, Morante Zaida, Aguilar Alfredo, Mas Luis A, Gomez Henry L, Vallejos Carlos S, Rolfo Christian, Pinto Joseph A
Unidad de Investigación Básica y Traslacional, Oncosalud-AUNA, San Borja, Lima 41, Peru.
Escuela de Medicina Humana, Universidad Privada San Juan Bautista, Chorrillos, Lima 09, Peru.
Oncotarget. 2016 Apr 12;7(15):20282-92. doi: 10.18632/oncotarget.7943.
There are different biological and clinical patterns of lung cancer between genders indicating intrinsic differences leading to increased sensitivity to cigarette smoke-induced DNA damage, mutational patterns of KRAS and better clinical outcomes in women while differences between genders at gene-expression levels was not previously reported. Here we show an enrichment of immune genes in NSCLC in women compared to men. We found in a GSEA analysis (by biological processes annotated from Gene Ontology) of six public datasets a repeated observation of immune gene sets enrichment in women. "Immune system process", "immune response", "defense response", "cellular defense response" and "regulation of immune system process" were the gene sets most over-represented while APOBEC3G, APOBEC3F, LAT, CD1D and CCL5 represented the top-five core genes. Characterization of immune cell composition with the platform CIBERSORT showed no differences between genders; however, there were differences when tumor tissues were compared to normal tissues. Our results suggest different immune responses in NSCLC between genders that could be related with the different clinical outcome.
肺癌在不同性别之间存在不同的生物学和临床模式，这表明内在差异导致女性对香烟烟雾诱导的DNA损伤、KRAS突变模式更为敏感，临床预后也更好，而此前尚未报道过性别在基因表达水平上的差异。在此，我们发现与男性相比，非小细胞肺癌（NSCLC）女性患者中免疫基因富集。我们在对六个公共数据集进行的基因集富集分析（GSEA，依据基因本体论注释的生物学过程）中反复观察到女性免疫基因集的富集。“免疫系统过程”“免疫反应”“防御反应”“细胞防御反应”和“免疫系统过程的调节”是最具代表性的基因集，而载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC3G）、载脂蛋白B mRNA编辑酶催化多肽样3F（APOBEC3F）、接头蛋白（LAT）、CD1d分子（CD1D）和趋化因子配体5（CCL5）是排名前五的核心基因。利用CIBERSORT平台对免疫细胞组成进行表征，结果显示不同性别之间无差异；然而，肿瘤组织与正常组织相比则存在差异。我们的结果表明，NSCLC在不同性别之间存在不同的免疫反应，这可能与不同的临床结局有关。
