Table_1_Gender Differential Transcriptome in Gastric and Thyroid Cancers.XLSX

Cancer has an important and considerable gender differential susceptibility confirmed by several epidemiological studies. Gastric (GC) and thyroid cancer (TC) are examples of malignancies with a higher incidence in males and females, respectively. Beyond environmental predisposing factors, it is expected that gender-specific gene deregulation contributes to this differential incidence. We performed a detailed characterization of the transcriptomic differences between genders in normal and tumor tissues from stomach and thyroid using Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) data. We found hundreds of sex-biased genes (SBGs). Most of the SBGs shared by normal and tumor belong to sexual chromosomes, while the normal and tumor-specific tend to be found in the autosomes. Expression of several cancer-associated genes is also found to differ between sexes in both types of tissue. Thousands of differentially expressed genes (DEGs) between paired tumor–normal tissues were identified in GC and TC. For both cancers, in the most susceptible gender, the DEGs were mostly under-expressed in the tumor tissue, with an enrichment for tumor-suppressor genes (TSGs). Moreover, we found gene networks preferentially associated to males in GC and to females in TC and correlated with cancer histological subtypes. Our results shed light on the molecular differences and commonalities between genders and provide novel insights in the differential risk underlying these cancers.

癌症的性别差异易感性显著，诸多流行病学研究所证实。胃（GC）癌和甲状腺癌（TC）分别以男性及女性中更高的发病率为例证。除环境易感因素外，性别特异性的基因失调亦被认为是造成这种差异发病率的重要原因。本研究对胃和甲状腺的正常及肿瘤组织中的转录组差异进行了细致的表征，数据来源于基因型-组织表达（GTEx）和癌症基因组图谱（TCGA）。我们发现数百个性别偏向基因（SBGs）。其中，正常和肿瘤组织中共同存在的SBGs多属性染色体，而正常和肿瘤特异性基因则更倾向于位于常染色体上。在两种组织类型中，癌症相关基因的表达也发现存在性别差异。在GC和TC中，对肿瘤-正常组织配对样本的差异表达基因（DEGs）进行了鉴定，数量达数千个。对于这两种癌症，在易感度最高的性别中，DEGs在肿瘤组织中普遍表现为低表达，且富含肿瘤抑制基因（TSGs）。此外，我们还发现GC中与男性相关、TC中与女性相关的基因网络，并与癌症的病理学亚型相关联。本研究揭示了性别之间的分子差异与共性，并为这些癌症背后的差异风险提供了新的见解。