从 Oncomine Comprehensive Assay Plus 预测同源重组缺陷并与 SOPHiA DDM HRD Solution 相关联。

Prediction of homologous recombination deficiency from Oncomine Comprehensive Assay Plus correlating with SOPHiA DDM HRD Solution.

机构信息

Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.

Department of Pathology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.

出版信息

PLoS One. 2024 Mar 25;19(3):e0298128. doi: 10.1371/journal.pone.0298128. eCollection 2024.

DOI:10.1371/journal.pone.0298128

PMID:38527014

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10962813/

Abstract

OBJECTIVE

Poly(ADP-ribose) polymerase (PARP) inhibitors are used for targeted therapy for ovarian cancer with homologous recombination deficiency (HRD). In this study, we aimed to develop a homologous recombination deficiency prediction model to predict the genomic integrity (GI) index of the SOPHiA DDM HRD Solution from the Oncomine Comprehensive Assay (OCA) Plus. We also tried to a find cut-off value of the genomic instability metric (GIM) of the OCA Plus that correlates with the GI index of the SOPHiA DDM HRD Solution.

METHODS

We included 87 cases with high-grade ovarian serous carcinoma from five tertiary referral hospitals in Republic of Korea. We developed an HRD prediction model to predict the GI index of the SOPHiA DDM HRD Solution. As predictor variables in the model, we used the HRD score, which included percent loss of heterozygosity (%LOH), percent telomeric allelic imbalance (%TAI), percent large-scale state transitions (%LST), and the genomic instability metric (GIM). To build the model, we employed a penalized logistic regression technique.

RESULTS

The final model equation is -21.77 + 0.200 × GIM + 0.102 × %LOH + 0.037 × %TAI + 0.261 × %LST. To improve the performance of the prediction model, we added a borderline result category to the GI results. The accuracy of our HRD status prediction model was 0.958 for the test set. The accuracy of HRD status using GIM with a cut-off value of 16 was 0.911.

CONCLUSION

The Oncomine Comprehensive Assay Plus provides a reliable biomarker for homologous recombination deficiency.

摘要

目的

聚（ADP-核糖）聚合酶（PARP）抑制剂被用于同源重组缺陷（HRD）的卵巢癌靶向治疗。在这项研究中，我们旨在开发一种同源重组缺陷预测模型，以预测来自 Oncomine 综合检测（OCA）Plus 的 SOPHiA DDM HRD Solution 的基因组完整性（GI）指数。我们还试图找到与 SOPHiA DDM HRD Solution 的 GI 指数相关的 OCA Plus 基因组不稳定性指标（GIM）的截止值。

方法

我们纳入了来自韩国 5 家三级转诊医院的 87 例高级别卵巢浆液性癌病例。我们开发了一种 HRD 预测模型，以预测 SOPHiA DDM HRD Solution 的 GI 指数。作为模型中的预测变量，我们使用了 HRD 评分，其中包括杂合性缺失率（%LOH）、端粒等位基因失衡率（%TAI）、大规模状态转换率（%LST）和基因组不稳定性指标（GIM）。为了构建模型，我们采用了惩罚逻辑回归技术。

结果

最终模型方程为-21.77+0.200×GIM+0.102×%LOH+0.037×%TAI+0.261×%LST。为了提高预测模型的性能，我们在 GI 结果中增加了一个边界结果类别。我们的 HRD 状态预测模型在测试集中的准确率为 0.958。GIM 截断值为 16 时，HRD 状态的准确率为 0.911。