Data_Sheet_2_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.

多项流行病学研究表明，癌症在性别上存在显著且不容忽视的易感差异。胃（GC）和甲状腺（TC）癌分别为男性与女性中发病率较高的恶性肿瘤。除环境易感因素外，性别特异的基因调控异常亦被预期为这种易感差异的成因之一。本研究利用基因型-组织表达（GTEx）和癌症基因组图谱（TCGA）数据，对胃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细致的描述。我们发现数百个性别偏向基因（SBGs）。正常组织和肿瘤组织中共享的SBGs大多属于性染色体，而特异于正常或肿瘤组织的SBGs则更常见于常染色体。在两种组织类型中，还发现了一些与性别相关的癌症相关基因表达存在差异。在GC和TC中，对配对的肿瘤-正常组织进行了数千个差异表达基因（DEGs）的鉴定。对于这两种癌症，在易感度较高的性别中，DEGs在肿瘤组织中的表达普遍降低，且富集于肿瘤抑制基因（TSGs）。此外，我们还发现，在GC中与男性相关的基因网络以及TC中与女性相关的基因网络与癌症的组织学亚型相关。本研究揭示了性别间的分子差异与共性，并为这些癌症背后的易感风险差异提供了新的见解。