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 MYC (22%), followed by NDRG1 (19%), ERBB2 (14%), PTEN (13%), PTGS2 (13%) and CDH1 (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.
Highlights
Cancer is one of the leading causes of death of women worldwide (Ferlay et al, 2015; Ginsburg et al, 2017)
A total of 128 (76 + 52) genes are common to breast, ovarian and cervical cancers; 141 (89 + 52) genes in breast, ovarian and endometrial cancers; 55 (3 + 52) genes in breast, cervical and endometrial cancers; 71 (17 + 52) genes in ovarian, endometrial and cervical cancers; 209 (81 + 76 + 52) genes in breast and cervical cancers; 174 (33 + 89 + 52) genes in breast and endometrial cancers; 528 (400 + 76 + 52) genes in breast and ovarian cancers; 205 (77 + 76 + 52) genes in ovarian and cervical cancers; 280 (139 + 89 + 52) genes in ovarian and endometrial cancers; and 64 (9 + 3 + 52) genes in endometrial and cervical cancers
We found that 141 genes in breast, ovarian and endometrial cancers (Fig. S2), which shows the same results we observed in four cancer analysis
Summary
Cancer is one of the leading causes of death of women worldwide (Ferlay et al, 2015; Ginsburg et al, 2017). Every year >2 million women are diagnosed with breast or cervical cancer, a large number remain undiagnosed (Ferlay et al, 2015). For 90% of breast cancer cases, women have an increased chance of survival for at least five more years, if diagnosed at an early stage of cancer development (American Chemical Society, 2018). In ovarian cancer, 5-year survival rates can increase from 5% to 90% with early detection (American Chemical Society, 2018). The reason behind this is that in the initial stages the cancer cells are confined to a small area and in a small number of cells, offers the best chance for effective treatment (Smith et al, 2003). Developing early detection tools may increase treatment options and result in an improved quality of life and survival rates for patients
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