Mitochondria in epithelial ovarian carcinoma exhibit abnormal phenotypes and blunted associations with biobehavioral factors.
Mitochondria in epithelial ovarian carcinoma exhibit abnormal phenotypes and blunted associations with biobehavioral factors.
复制标题
上皮卵巢癌中的线粒体表现出异常的表型和与生物行为因子的钝化关联。
DOI：
10.1038/s41598-021-89934-6
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发表时间：
2021-06-02
影响因子：
4.6
通讯作者：
Picard M
中科院分区：
文献类型：
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作者：
Bindra S;McGill MA;Triplett MK;Tyagi A;Thaker PH;Dahmoush L;Goodheart MJ;Ogden RT;Owusu-Ansah E;R Karan K;Cole S;Sood AK;Lutgendorf SK;Picard M
恶性肿瘤细胞表现出线粒体改变，也受到生物行为过程的影响，但生物行为因素和线粒体在恶性肿瘤中的交叉作用仍未被探索。在此，我们检测了良性组织和高级别上皮性卵巢癌（EOC）中线粒体含量和功能的多种生化和分子标记，并对生物行为因素进行了探索性分析。首先，对公开数据库（n = 1435）的分析表明，EOC中特定线粒体蛋白的基因表达与存活相关。通过对51例良性卵巢肿块患者和128例高级别卵巢肿块患者组织中线粒体含量和功能的多种生化和分子标记进行定量分析，结果显示，与良性卵巢肿块相比，卵巢肿块组织中线粒体含量和呼吸链酶活性高3.3 - 8.4倍（P < 0.001），但线粒体DNA （mtDNA）水平相似（−3.1%），表明卵巢肿块组织中线粒体表型异常。线粒体呼吸链活性也与腹水中白细胞介素-6 （IL-6）水平有关。在良性组织中，负性生物行为因素与线粒体含量和呼吸链活性呈负相关，而正性生物行为因素往往与线粒体测量呈正相关，尽管效应大小为小到中等（r = - 0.43至0.47）。相比之下，严重的EOCs表现出不太明显的生物行为-线粒体相关性。这些结果证明了EOC中线粒体功能表型异常，并为进一步研究生物行为因素与癌症线粒体之间的联系提供了依据。
Malignant tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and mitochondria in malignant tumors remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign tissue and in high-grade epithelial ovarian carcinoma (EOC) in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n = 1435) showed that gene expression of specific mitochondrial proteins in EOC is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in tissue from 51 patients with benign ovarian masses and 128 patients with high-grade EOC revealed that compared to benign tissue, EOCs exhibit 3.3–8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P < 0.001) but similar mitochondrial DNA (mtDNA) levels (− 3.1%), documenting abnormal mitochondrial phenotypes in EOC. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r = − 0.43 to 0.47). In contrast, serous EOCs showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in EOC and warrant further research on the link between biobehavioral factors and mitochondria in cancer.