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对女性四种癌症中与激素刺激相关的常见基因和驱动突变的综合分析。

Integrative analysis of common genes and driver mutations implicated in hormone stimulation for four cancers in women.

作者信息

Bhyan Salma Begum, Wee YongKiat, Liu Yining, Cummins Scott, Zhao Min

机构信息

Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sunshine Coast, QLD, Australia.

The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China.

出版信息

PeerJ. 2019 Jun 6;7:e6872. doi: 10.7717/peerj.6872. eCollection 2019.

Abstract

Cancer is one of the leading cause of death of women worldwide, and breast, ovarian, endometrial and cervical cancers contribute significantly to this every year. Developing early genetic-based diagnostic tools may be an effective approach to increase the chances of survival and provide more treatment opportunities. However, the current cancer genetic studies are mainly conducted independently and, hence lack of common driver genes involved in cancers in women. To explore the potential common molecular mechanism, we integrated four comprehensive literature-based databases to explore the shared implicated genetic effects. Using a total of 460 endometrial, 2,068 ovarian, 2,308 breast and 537 cervical cancer-implicated genes, we identified 52 genes which are common in all four types of cancers in women. Furthermore, we defined their potential functional role in endogenous hormonal regulation pathways within the context of four cancers in women. For example, these genes are strongly associated with hormonal stimulation, which may facilitate rapid diagnosis and treatment management decision making. Additional mutational analyses on combined the cancer genome atlas datasets consisting of 5,919 gynaecological and breast tumor samples were conducted to identify the frequently mutated genes across cancer types. For those common implicated genes for hormonal stimulants, we found that three quarter of 5,919 samples had genomic alteration with the highest frequency in (22%), followed by (19%), (14%), (13%), (13%) and (11%). We also identified 38 hormone related genes, eight of which are associated with the ovulation cycle. Further systems biology approach of the shared genes identified 20 novel genes, of which 12 were involved in the hormone regulation in these four cancers in women. Identification of common driver genes for hormone stimulation provided an unique angle of involving the potential of the hormone stimulants-related genes for cancer diagnosis and prognosis.

摘要

癌症是全球女性主要死因之一,每年乳腺癌、卵巢癌、子宫内膜癌和宫颈癌对此有显著“贡献”。开发早期基于基因的诊断工具可能是增加生存几率并提供更多治疗机会的有效方法。然而,目前的癌症基因研究主要是独立进行的,因此缺乏涉及女性癌症的常见驱动基因。为了探索潜在的共同分子机制,我们整合了四个基于文献的综合数据库,以探究共享的相关基因效应。利用总共460个与子宫内膜癌、2068个与卵巢癌、2308个与乳腺癌以及537个与宫颈癌相关的基因,我们鉴定出52个在所有四种女性癌症类型中都常见的基因。此外,我们在女性四种癌症的背景下定义了它们在内源性激素调节途径中的潜在功能作用。例如,这些基因与激素刺激密切相关,这可能有助于快速诊断和治疗管理决策。我们还对由5919个妇科和乳腺肿瘤样本组成的癌症基因组图谱数据集进行了额外的突变分析,以确定不同癌症类型中频繁突变的基因。对于那些与激素刺激相关的常见基因,我们发现5919个样本中有四分之三发生了基因组改变,其中频率最高的是(22%),其次是(19%)、(14%)、(13%)、(13%)和(11%)。我们还鉴定出38个与激素相关的基因,其中8个与排卵周期有关。对共享基因的进一步系统生物学方法鉴定出20个新基因,其中12个参与了这四种女性癌症中的激素调节。鉴定激素刺激的共同驱动基因为涉及激素刺激相关基因在癌症诊断和预后方面的潜力提供了一个独特视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e18/6556371/980684f58c9c/peerj-07-6872-g001.jpg

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