Biomarkers and Strategies for Early Detection of Ovarian Cancer.
Biomarkers and Strategies for Early Detection of Ovarian Cancer.
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生物标志物和早期发现卵巢癌的策略。
DOI：
10.1158/1055-9965.epi-20-1057
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Skates SJ
中科院分区：
文献类型：
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作者：
Bast RC Jr;Lu Z;Han CY;Lu KH;Anderson KS;Drescher CW;Skates SJ
卵巢癌的早期发现仍然是一个重要的未得到满足的医疗需求。有效的筛查可以将死亡率降低10%-30%。单独使用，无论是血清CA125还是经阴道超声(TVS)都不够敏感或特异。事实证明，两种分期策略更有效，当女性的CA125显著高于基线水平时，会提示电视，而异常的超声图会提示手术。两个主要的筛查试验已经证明，这种策略具有足够的特异性，但对早期(I-II)疾病的敏感性必须提高，才能对死亡率产生更大的影响。为了改进第一阶段，不同的蛋白质生物标志物小组检测到了CA125遗漏的病例。抗TP53自身抗体在CA125升高前8个月和临床诊断前22个月检测到20%的早期卵巢癌。正在对自身抗体和抗原-自身抗体复合体进行评估，目标是单独检测或联合CA125检测90%的早期卵巢癌，同时保持对照对象98%的特异性。其他生物标志物，包括微RNA、ctDNA、甲基化DNA和ctDNA改变的组合正在进行测试，以提供最佳的第一阶段测试。人们还在开发比电视更灵敏的新技术，以成像小体积的肿瘤。
Early detection of ovarian cancer remains an important unmet medical need. Effective screening could reduce mortality by 10-30%. Used individually, neither serum CA125 nor transvaginal sonography (TVS) is sufficiently sensitive or specific. Two stage strategies have proven more effective, where a significant rise above a woman’s baseline CA125 prompts TVS and an abnormal sonogram prompts surgery. Two major screening trials have documented that this strategy has adequate specificity, but sensitivity for early stage (I-II) disease must improve to have a greater impact on mortality. To improve the first stage, different panels of protein biomarkers have detected cases missed by CA125. Autoantibodies against TP53 have detected 20% of early stage ovarian cancers 8 months prior to elevation of CA125 and 22 months prior to clinical diagnosis. Panels of autoantibodies and antigen-autoantibody complexes are being evaluated with the goal of detecting >90% of early stage ovarian cancers, alone or in combination with CA125, while maintaining 98% specificity in control subjects. Other biomarkers, including micro-RNAs, ctDNA, methylated DNA, and combinations of ctDNA alterations are being tested to provide an optimal first stage test. New technologies are also being developed with greater sensitivity than TVS to image small volumes of tumor.