Racial/ethnic differences in functional metabolites among ovarian cancer patients

摘要 卵巢癌是最致命的妇科癌症，有21,000例病例和14,000例死亡 预计将于2021年在美国发生。黑人女性患卵巢癌的5年生存率最低 白人女性为36%，而白人女性为46%。卵巢癌的这种显著的种族差异持续存在，即使在 不同种族或具有相似社会经济地位的患者在获得医疗保健方面没有差异， 从而证明有必要探索潜在的潜在生物学机制。阴道微生物群是一种 这种机制可能是卵巢癌存活率和疾病严重程度人群差异的基础 通过代谢产物创造和维持炎症性肿瘤微环境的潜力 制作。在黑人中，缺乏乳杆菌的阴道微生物群落往往很常见 女性，其特点是抗菌素代谢物水平降低，炎症水平升高- 诱导脂质，以及氨基酸代谢变化的产物。此外，主要贡献来源是 全身炎症，卵巢癌的已知危险因素，如盆腔炎疾病，滑石粉 暴露和肥胖在黑人女性中往往更普遍。有鉴于乳酸菌很差的阴道 微生物群在黑人女性中更常见，重要的是了解种族差异 在阴道中，微生物群的组成转化为功能差异，从而对肿瘤产生影响 微环境，并促进全身炎症。在这个拟议的项目中，我们将评估差异 黑色卵巢与白色卵巢宫颈阴道液中抗微生物和致炎代谢产物的比较 癌症患者。我们还将评估全身炎症标志物的种族差异以及 全身炎症标志物与阴道微生物功能代谢产物的关系。 这项研究的发现将为关于特定生物学机制的假说的产生提供信息 可能是卵巢癌健康结局差异的基础，为进一步研究提供了基础。另外， 它将提供信息，阐明某些新兴治疗方法的潜力 以帮助缩小黑人女性的卵巢结局差异。

ABSTRACT Ovarian cancer is the most lethal gynecological cancer with 21,000 incident cases and 14,000 deaths projected to occur in the US in 2021. Black women have the lowest 5-year survival rates for ovarian cancer of 36% compared to 46% for White women. This marked racial disparity in ovarian cancer persists even when there is no difference in access to healthcare among races or among patients of similar socioeconomic status, thus justifying a need to probe potential underlying biological mechanisms. The vaginal microbiome is one such mechanism that may underlie population differences in ovarian cancer survival and disease severity due to its potential for creating and sustaining an inflammatory tumor micro-environment through metabolite production. Vaginal microbial communities that are Lactobacillus-poor tend to be common among Black women, and are characterized by reduced levels of antimicrobial metabolites, higher levels of inflammation- inducing lipids, and products from altered amino acid metabolism. Moreover, major contributing sources to systemic inflammation, a known risk factor for ovarian cancer, such as pelvic inflammation disorder, talc exposure, and obesity, tend to be more prevalent among Black women. Given that Lactobacillus-poor vaginal microbiomes are more common among Black women, it is important to understand whether racial differences in vaginal microbiome composition translate to functional differences that can exert effects on the tumor microenvironment and contribute to systemic inflammation. In this proposed project, we will assess differences in anti-microbial and inflammation-inducing metabolites within cervicovaginal fluid of Black vs. White ovarian cancer patients. We will also evaluate racial differences in markers of systemic inflammation and the relationship between markers of systemic inflammation and functional metabolites of vaginal microbiome. Findings from this study would inform the generation of hypotheses on specific biological mechanisms that might underlie disparities in ovarian cancer health outcomes, providing the basis for further investigation. Also, it would provide information that would shed light on the potential for certain emerging therapeutic approaches to help bridge ovarian outcome disparities for Black women.