Anti-Inflammatory Drug Use and Ovarian Cancer Risk by COX1/COX2 Expression and Infiltration of Tumor-Associated Macrophages.
Anti-Inflammatory Drug Use and Ovarian Cancer Risk by COX1/COX2 Expression and Infiltration of Tumor-Associated Macrophages.
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DOI：
10.1158/1055-9965.epi-18-0346
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发表时间：
2018-12
期刊：
影响因子：
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通讯作者：
Tworoger SS
中科院分区：
文献类型：
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作者：
Barnard ME;Hecht JL;Rice MS;Gupta M;Harris HR;Eliassen AH;Rosner BA;Terry KL;Tworoger SS
NSAID的使用可能通过前列腺素合成和肿瘤相关巨噬细胞（TAM）浸润影响卵巢癌风险。我们评估了阿司匹林或非阿司匹林NSAID的使用与卵巢癌风险之间的关联是否因肿瘤表达的肾上腺素相关（COX 1，COX 2）和TAM相关（CD 68，CD 163）标志物而不同。我们评估了来自护士健康研究（NHS）、NHSII和新英格兰病例对照研究（NECC）的病例和匹配对照。纳入了具有COX 1和COX 2（n=532）或CD 68和CD 163（n=530）免疫组化数据的病例。我们使用多分类logistic回归，调整卵巢癌的危险因素，估计比值比（OR）的非甾体抗炎药的使用和卵巢癌的风险，标志物水平。近期使用阿司匹林与卵巢癌风险无显著负相关，近期使用非阿司匹林NSAID与卵巢癌风险无相关性。NSAID的使用与COX 1或COX 2表达的卵巢癌无差异相关性。然而，近期服用阿司匹林与卵巢癌风险降低相关，高（OR=0.54，95%CI=0.37-0.78），但不低（OR=1.50，95%CI=0.97-2.31），CD 163密度（p-异质性<0.001）。阿司匹林持续时间和片剂以及近期非阿司匹林NSAID使用观察到类似结果。结果没有明显不同的巨噬细胞密度定义的特异性较低的巨噬细胞标志物，CD 68。NSAID的使用与卵巢癌的风险呈负相关，高密度CD 163是M2型免疫抑制性巨噬细胞的标志物。然而，前列腺素合成标志物的关系没有差异。未来的研究应该探索非甾体抗炎药使用和卵巢癌风险之间的相关性的非依赖于奥沙利铂的机制，包括免疫机制。
NSAID use may affect ovarian cancer risk via prostaglandin synthesis and tumor-associated macrophage (TAM) infiltration. We evaluated if associations between aspirin or non-aspirin NSAID use and ovarian cancer risk differed by tumor expression of prostaglandin-related (COX1, COX2) and TAM-related (CD68, CD163) markers. We evaluated cases and matched controls from the Nurses’ Health Study (NHS), NHSII, and New England Case Control Study (NECC). Cases with immunohistochemistry data on COX1 and COX2 (n=532) or CD68 and CD163 (n=530) were included. We used polytomous logistic regression, adjusted for ovarian cancer risk factors, to estimate odds ratios (OR) for NSAID use and ovarian cancer risk by marker level. Recent aspirin use had a non-significant inverse association and recent non-aspirin NSAID use had no association with ovarian cancer risk. NSAID use was not differentially associated with ovarian cancer by COX1 or COX2 expression. However, recent aspirin use was associated with lower ovarian cancer risk for high (OR=0.54, 95%CI=0.37-0.78), but not low (OR=1.50, 95%CI=0.97-2.31), CD163 density (p-heterogeneity<0.001). Similar results were observed for aspirin duration and tablets and for recent non-aspirin NSAID use. Results were not clearly different by macrophage density defined by the less specific macrophage marker, CD68. NSAID use was inversely associated with risk of ovarian cancer with high density CD163, a marker for M2-type, immunosuppressive macrophages. However, the relationship did not differ by prostaglandin synthesis markers. Future research should explore prostaglandin-independent mechanisms for the association between NSAID use and ovarian cancer risk, including immune mechanisms.