Ovarian Cancer Detection with Blood- and Imaging-Based Biomarkers

项目总结 这项申请是为了支持博士后研究生Dominique Galvez女士通过多样性 R01CA260399的补充说明。Galvez女士将直接支持和扩大具体目标2：发展 内窥镜成像和病理组学标记物，推动进展并扩大她的培训。 卵巢癌的一个中心问题是诊断迟缓，这会导致5年存活率直线下降。 低于50%。由于卵巢癌是如此致命，降低风险的输卵管卵巢切除术(RRSO)通常是 建议高危妇女使用；然而，RRSO具有生育和健康后果。现在是时候了 认为卵巢高级别浆液性癌(HGSC)可能起源于输卵管(FTs)浆液性癌 输卵管上皮内癌(STIC)。我们的初步数据显示，血清中有显著变化 HGSC患者确诊前12-84个月的蛋白质生物标志物。此外，我们还展示了这种变化 在正常和癌变的卵巢和FTs的多光谱荧光图像标记物中，我们可以 建立一个薄薄的输卵管镜，适合于横穿子宫和FT进行成像和细胞采集。 我们将满足临床上对STIC和早期(I/II期)卵巢微创检测的需求 癌症。目前，还没有一种方法能够检测出提前12个月以上的卵巢HGSC。 总体而言，我们的工作将满足及早发现侵袭性癌症的需要。我们会 结合血液蛋白质标志物筛查和微创输卵管镜光学成像和FT 收集细胞。我们的手术将在一项对接受双侧输卵管手术的高危女性的研究中进行测试。 卵巢切除和子宫切除，这将使我们能够获得并将检测结果与黄金标准进行比较 组织学。具体目标是： 1)开发和验证检测STIC和早期上皮性卵巢癌的生物标志物。我们会改进的 在现有的基于截断的算法的基础上，结合新发现的标记，提出了一种基于速度的 生物标记算法。在诊断前12-84个月检测到疾病的算法将在 一组独立的、盲目的临床血液样本。 2)发展内窥镜影像和病理组学标记物。我们将改进我们的输卵管镜原型 该系统具有更高的分辨率多光谱成像和改进的细胞采集能力。我们将发展 从FT图像和收集的细胞中提取成像和核计量标记，并进行体内试验。 3)制定可操作的临床策略，以早期发现卵巢上皮癌。一项研究将是 在计划进行RRSO的高危女性中进行。那些血液检测呈阳性的人将会 让他们的组织接受输卵管镜检查。成像和病理组学数据将用于开发分类器， 这将与正常FT、STIC或隐匿性HGSC的金标准组织学结果进行比较。

PROJECT SUMMARY This application is to support a predoctoral graduate student, Ms. Dominique Galvez, through a diversity supplement to R01CA260399. Ms. Galvez will directly support and expand upon Specific Aim 2: Develop endoscopic imaging and pathomics markers, advancing progress as well as expanding her training. A central problem in ovarian cancer is late diagnosis, which causes the 5-year survival rate to plummet below 50%. Because ovarian cancer is so deadly, risk-reducing salpingo-oophorectomy (RRSO) is often recommended for women at high risk; however, RRSO has fertility and health consequences. It is now believed that ovarian high-grade serous carcinoma (HGSC) may begin in the fallopian tubes (FTs) as serous tubal intraepithelial carcinoma (STIC). Our preliminary data indicate that there are significant changes in serum protein biomarkers in HGSC cases 12-84 months prior to diagnosis. Further, we have also shown that changes occur in multispectral fluorescence image markers of normal and cancerous ovaries and FTs, and that we can build a thin falloposcope suitable for traversing the uterus and FT for imaging and cell collection. We will address the unmet clinical need for a minimally invasive test for STIC and early (stage I/II) ovarian cancer. Currently, no methods enable the detection of ovarian HGSC with a lead time of more than 12 months. Overall, our work will meet the need to detect aggressive cancers at the earliest possible stage. We will combine blood screening for protein markers with a minimally invasive falloposcopy for optical imaging and FT cell collection. Our procedure will be tested in a study of women at high risk undergoing bilateral salpingo- oophorectomy with hysterectomy, which will enable us to obtain and compare test results to gold standard histology. The specific aims are to: 1) Develop and validate biomarkers that detect STIC and early epithelial ovarian cancer. We will improve upon our existing cut-off based algorithm with newly-discovered markers as well develop a velocity-based biomarker algorithm. The algorithm that detects disease 12-84 months prior to diagnosis will be confirmed in an independent, blinded set of clinical blood samples. 2) Develop endoscopic imaging and pathomics markers. We will improve our prototype falloposcope system with higher resolution multispectral imaging and improved cell collection ability. We will develop imaging and karyometric markers from the FT images and the cells collected, and perform a pilot in vivo study. 3) Develop an actionable clinical strategy for early detection of epithelial ovarian cancer. A study will be performed in women at high risk who are planning a RRSO. Those who test positive from our blood test will have their tissue undergo a falloposcopy. Imaging and pathomics data will be used to develop a classifier, which will be compared to gold standard histology findings of normal FT, STIC, or occult HGSC.