TNF-α expression, risk factors, and inflammatory exposures in ovarian cancer: evidence for an inflammatory pathway of ovarian carcinogenesis?
TNF-α expression, risk factors, and inflammatory exposures in ovarian cancer: evidence for an inflammatory pathway of ovarian carcinogenesis?
复制标题
DOI：
10.1016/j.humpath.2016.03.006
复制
发表时间：
2016-08
期刊：
影响因子：
3.3
通讯作者：
Terry K
中科院分区：
文献类型：
--
作者：
Gupta M;Babic A;Beck AH;Terry K
炎症细胞因子，如肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6），在卵巢癌中升高。细胞因子表达的组织学亚型或卵巢癌危险因素的差异可以提供有用的洞察卵巢癌的风险和病因。我们采用核糖核酸（RNA）原位杂交技术对78例上皮性卵巢癌（51例浆液性、12例类浆液性、7例透明细胞性、2例粘液性、6例其他）组织芯片切片中TNF-α和IL-6的表达进行了评估，这些上皮性卵巢癌来自一项基于人群的病例对照研究。对细胞因子表达进行半定量评分，并使用多分类logistic回归计算比值比（OR）和95%置信区间（CI）。TNF-α在46%的肿瘤中表达，而IL-6仅在18%的肿瘤中稀疏表达。对于这两种标志物，表达最常见于高级别浆液性癌，其次是类浆液性癌。产次与TNF-α阳性肿瘤的风险降低相关（OR=0.3，95%CI：3名或以上儿童与无儿童相比为0.1-0.7），但与TNF-α阴性肿瘤的风险降低无关（p-异质性=0.02）。相比之下，目前吸烟与TNF-α阴性（OR=2.8，95% CI：1.2，6.6）而非TNF-α阳性肿瘤（p-异质性= 0.06）的风险增加近3倍相关。我们的数据表明TNF-α在卵巢癌中的表达因组织学亚型而异，并为炎症在卵巢癌发生中的作用提供了一些支持。我们研究中发现的新关联需要在未来的研究中在更大的患者队列中进行验证。
Inflammatory cytokines, like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), are elevated in ovarian cancer. Differences in cytokine expression by histologic subytpe or ovarian cancer risk factors can provide useful insight into ovarian cancer risk and etiology. We used ribonucleic acid (RNA) in-situ hybridization to assess TNF-α and IL-6 expression on tissue microarray slides from 78 epithelial ovarian carcinomas (51 serous, 12 endometrioid, 7 clear cell, 2 mucinous, 6 other) from a population-based case control study. Cytokine expression was scored semi-quantitatively and odds ratios (OR) and 95% confidence intervals (CI) were calculated using polytomous logistic regression. TNF-α was expressed in 46% of the tumors while sparse IL-6 expression was seen only 18% of the tumors. For both markers, expression was most common in high grade serous carcinomas followed by endometrioid carcinomas. Parity was associated with a reduced risk of TNF-α positive (OR=0.3, 95% CI: 0.1-0.7 for 3 or more children versus none) but not TNF-α negative tumors (p-heterogeneity=0.02). In contrast, current smoking was associated with a nearly three fold increase in risk of TNF-α negative (OR=2.8, 95% CI: 1.2, 6.6) but not TNF-α positive tumors (p-heterogeneity = 0.06). Our data suggests that TNF-α expression in ovarian carcinoma varies by histologic subtype and provides some support for the role of inflammation in ovarian carcinogenesis. The novel associations detected in our study need to be validated in a larger cohort of patients in future studies.