PO.PS01.01 · 人群科学
丧偶与卵巢肿瘤基因表达之间的关联
Association between widowhood and ovarian tumor gene expression
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：应激增加发生上皮性卵巢癌（EOC）的风险。这可导致交感神经系统（SNS）激活和去甲肾上腺素（NE）释放。NE促进炎症、血管生成和细胞运动性，从而影响肿瘤进展的早期和晚期。丧偶是一种慢性社会心理应激形式，与EOC风险增加相关。我们假设，在EOC诊断前经历丧偶的女性，与已婚女性相比，其肿瘤中炎症相关通路和免疫抑制通路的基因表达更高。
方法：对来自护士健康研究（NHS）、NHSII和新英格兰病例对照研究中167例高级别浆液性或低分化卵巢癌肿瘤（这些患者具有诊断前婚姻状态信息）进行了RNA测序。主要暴露为诊断前1年内曾报告过丧偶。采用线性回归识别与丧偶相关的差异表达基因，并对年龄进行校正。采用基因集富集分析（GSEA），使用Cancer Hallmarks、KEGG和Reactome数据库识别与丧偶相关的生物学通路。
结果：五个基因（KCNE3、ACHE、C3orf52、RPL19P9和AC116366）在丧偶个体相较已婚个体的卵巢肿瘤中显著上调。上调最显著的基因与伤口愈合和癌症进展相关。两个基因（GABBR2和RPS3AP29）显著下调，已被证明参与抑制性神经传递和肿瘤免疫细胞浸润升高。GSEA识别出六条与丧偶表现出显著关联的通路，特别是与炎症（TNF-α）、增殖（G2M检查点）和肿瘤免疫（干扰素-α和干扰素-γ应答）相关的通路。
结论：我们的结果为将丧偶与卵巢癌发生联系起来的生物学通路提供了见解，特别是通过炎症和肿瘤免疫通路。
查看英文原文 English abstract
Background: Distress increases the risk of developing epithelial ovarian cancer (EOC). This can lead to the activation of the sympathetic nervous system (SNS) and the release of norepinephrine (NE). NE promotes inflammation, angiogenesis, and cell motility, which influence early and late stages of tumor progression. Widowhood is one form of chronic psychosocial stress that is associated with an increase in EOC risk. We hypothesize that women who experienced widowhood prior to EOC diagnosis will have higher tumor gene expression of inflammation-related and immune suppression pathways when compared to women who are married.
Methods: RNA sequencing was performed on 167 high-grade serous or poorly differentiated ovarian cancer tumors from the Nurses' Health Study (NHS), NHSII, and the New England Case-Control study who had information on pre-diagnosis marital status. The primary exposure was ever reported widowhood up to 1 year before diagnosis. Linear regression was used to identify differentially expressed genes associated with widowhood, adjusted for age. Gene set enrichment analysis (GSEA) using the Cancer Hallmarks, KEGG, and Reactome databases was employed to identify biological pathways associated with widowhood.
Results: Five genes (KCNE3, ACHE, C3orf52, RPL19P9, and AC116366) were significantly upregulated in the ovarian tumors of widowed versus married individuals. The top upregulated genes are associated with wound healing and cancer progression. Two genes (GABBR2 and RPS3AP29) were significantly downregulated and have been demonstrated to be involved in inhibitory neurotransmission and elevated tumor immune cell infiltration. GSEA identified six pathways that exhibited significant associations with widowhood, specifically related to inflammation (TNF-alpha), proliferation (G2M checkpoint), and tumor immunity (interferon-alpha and gamma response).
Conclusions: Our results provide insight into biological pathways that link widowhood to ovarian cancer development, particularly through inflammatory and tumor immunity pathways.
利益披露 Disclosure
J. Perez Morales, None..
K. Berns, None..
C. Copp, None..
J. Grieco, None.