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预测晚期原发性高级别浆液性卵巢癌患者手术结局的生物标志物。我们做到了吗?卵巢癌前瞻性生物库分析。

Predictive biomarker for surgical outcome in patients with advanced primary high-grade serous ovarian cancer. Are we there yet? An analysis of the prospective biobank for ovarian cancer.

机构信息

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Gynecology, Augustenburger Platz 1, 13353 Berlin, Germany; Tumor Bank Ovarian Cancer, ENGOT Biobank, Charité Medizinische Universität Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Gynecology, Augustenburger Platz 1, 13353 Berlin, Germany; Tumor Bank Ovarian Cancer, ENGOT Biobank, Charité Medizinische Universität Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

出版信息

Gynecol Oncol. 2022 Aug;166(2):334-343. doi: 10.1016/j.ygyno.2022.06.010. Epub 2022 Jun 21.

Abstract

BACKGROUND

High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer and is associated with high mortality rates. Surgical outcome is one of the most important prognostic factors. There are no valid biomarkers to identify which patients may benefit from a primary debulking approach.

OBJECTIVE

Our study aimed to discover and validate a predictive panel for surgical outcome of residual tumor mass after first-line debulking surgery.

STUDY DESIGN

Firstly, "In silico" analysis of publicly available datasets identified 200 genes as predictors for surgical outcome. The top selected genes were then validated using the novel Nanostring method, which was applied for the first time for this particular research objective. 225 primary ovarian cancer patients with well annotated clinical data and a complete debulking rate of 60% were compiled for a clinical cohort. The 14 best rated genes were then validated through the cohort, using immunohistochemistry testing. Lastly, we used our biomarker expression data to predict the presence of miliary carcinomatosis patterns.

RESULTS

The Nanostring analysis identified 37 genes differentially expressed between optimal and suboptimal debulked patients (p < 0.05). The immunohistochemistry validated the top 14 genes, reaching an AUC Ø0.650. The analysis for the prediction of miliary carcinomatosis patterns reached an AUC of Ø0.797.

CONCLUSION

The tissue-based biomarkers in our analysis could not reliably predict post-operative residual tumor. Patient and non-patient-associated co-factors, surgical skills, and center experience remain the main determining factors when considering the surgical outcome at primary debulking in high-grade serous ovarian cancer patients.

摘要

背景

高级别浆液性卵巢癌(HGSOC)是最常见的卵巢癌亚型,与高死亡率相关。手术结果是最重要的预后因素之一。目前尚无有效的生物标志物来识别哪些患者可能从初始减瘤手术中获益。

目的

我们的研究旨在发现和验证一个预测一线减瘤手术后残余肿瘤质量手术结果的预测面板。

研究设计

首先,通过对公开数据集的“计算”分析,确定了 200 个基因作为手术结果的预测因子。然后,使用新的 Nanostring 方法对这些顶级基因进行验证,这是该特定研究目标首次应用该方法。我们汇集了 225 名具有良好注释临床数据和 60%完全减瘤率的原发性卵巢癌患者作为临床队列。然后,通过免疫组织化学检测,在队列中验证了前 14 个最佳评分基因。最后,我们使用我们的生物标志物表达数据来预测微转移癌模式的存在。

结果

Nanostring 分析确定了 37 个在最佳减瘤和次优减瘤患者之间表达差异的基因(p < 0.05)。免疫组织化学验证了前 14 个基因,达到 AUC Ø0.650。分析预测微转移癌模式的 AUC 达到 Ø0.797。

结论

我们分析中的组织生物标志物不能可靠地预测术后残余肿瘤。在考虑高级别浆液性卵巢癌患者初始减瘤手术的手术结果时,患者和非患者相关的共同因素、手术技能和中心经验仍然是主要决定因素。

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