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首页> 外文期刊>PLoS Genetics >Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
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Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry

机译：主要的非洲或欧洲遗传血统中前列腺癌患者基因组和转录组景观的综合比较

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Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10 ~(?03)), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10 ~(?02)), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10 ~(?03)). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10 ~(?48)). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10 ~(?125)). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1 , PCAT1 and PCAT10/CTBP1-AS , were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes.
机译：主要是非洲血统（AA）的男性具有更高的前列腺癌（帽）发病率和比主要欧洲祖先（EA）的男性更差的存活率。虽然社会经济因素驱动这种差异，但基因组因子也可能有助于发病率和死亡率的差异。为了通过患者遗传血统比较前列腺肿瘤基因组改变和转录组谱的患病率，我们评估了来自癌症基因组地图集（​​TCGA）帽队（N = 498）的基因组谱。通过使用基因分型数据计算算法估算患者全球和局部遗传血统; 414（83.1％）是EA，61（12.2％）是AA，11（2.2％）是东亚血统（EAA），10（2.0％）是美洲原住民（NA），2（0.4％）是其他祖先。遗传血统与自我识别的种族/种族非常一致。随后的分析限于61AA和414 ea病例。血管突变频率的血液（20.3％AA与10.0％EA; P = 5.6×10〜（β03）），TMPRSS2-ERG融合（29.3％AA与39.6％EA; P = 4.4×10〜（Δ02））和PTEN缺失/损失（11.5％AA与30.2％EA; P = 3.5×10〜（？03））。 AAS和EA之间的差异表达基因（DEGS）显示出对前列腺EQT1靶基因的显着富集（P = 8.09×10〜（α48））。在AAS中观察到对免疫相关途径的高度表达的DEGS的富集，并且在EA中进行PTEN / PI3K信号传导。近三分之一的含量（31.3％）是长期非编码RNA（DE-LNCRNA）。在AAs中具有更高表达的DE-LNCRNA的比例大大超过了AAs中的较低表达（P = 1.2×10〜（？125））。芯片-SEQ和RNA-SEQ数据都表明DE-LNCRNA与非DE-LNCRNA中的AR信号传导途径的强大调节作用。帽相关的致癌LNCRNA，如PVT1，PCAT1和PCAT10 / CTBP1-ov，以AAS更高度表达。我们在EA和AA之间报告了前列腺肿瘤基因组和转录组中的大量异质性。这些差异可能是帽发病率和结果中的种族差异的生物学贡献者。

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