Data_Sheet_1_Gender Differential Transcriptome in Gastric and Thyroid Cancers.pdf

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.

癌症在性别差异易感性方面具有重要且显著的差异，这一结论已由多项流行病学研究得到证实。胃癌（GC）和甲状腺癌（TC）分别为男性与女性中发病率较高的恶性肿瘤。除了环境易感因素外，性别特异的基因失调预计也是导致这种差异发生的原因之一。我们利用基因型-组织表达（GTEx）和癌症基因组图谱（TCGA）数据，对胃部和甲状腺的正常及肿瘤组织中性别间的转录组差异进行了详细分析。我们发现了数百个性别偏向基因（SBGs）。大部分正常和肿瘤组织中共有的SBGs归属于性染色体，而正常和肿瘤特异性SBGs则倾向于存在于常染色体上。同时，在两种组织类型中，多种与癌症相关的基因表达也被发现存在性别差异。在胃癌和甲状腺癌中，对肿瘤-正常组织配对中识别出的数千个差异表达基因（DEGs）进行了研究。对于这两种癌症，在易感性别中，DEGs在肿瘤组织中大多表现为低表达，且富含肿瘤抑制基因（TSGs）。此外，我们还在胃癌中发现了与男性相关、在甲状腺癌中发现了与女性相关的基因网络，并与其癌症组织学亚型相关联。我们的研究揭示了性别间分子差异与共性的本质，并为这些癌症背后差异风险的潜在机制提供了新的见解。