Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
BMC Med. 2020 Aug 18;18(1):236. doi: 10.1186/s12916-020-01684-w.
Ovarian cancer causes 151,900 deaths per year worldwide. Treatment and prognosis are primarily determined by the histopathologic interpretation in combination with molecular diagnosis. However, the relationship between histopathology patterns and molecular alterations is not fully understood, and it is difficult to predict patients' chemotherapy response using the known clinical and histological variables.
We analyzed the whole-slide histopathology images, RNA-Seq, and proteomics data from 587 primary serous ovarian adenocarcinoma patients and developed a systematic algorithm to integrate histopathology and functional omics findings and to predict patients' response to platinum-based chemotherapy.
Our convolutional neural networks identified the cancerous regions with areas under the receiver operating characteristic curve (AUCs) > 0.95 and classified tumor grade with AUCs > 0.80. Functional omics analysis revealed that expression levels of proteins participated in innate immune responses and catabolic pathways are associated with tumor grade. Quantitative histopathology analysis successfully stratified patients with different response to platinum-based chemotherapy (P = 0.003).
These results indicated the potential clinical utility of quantitative histopathology evaluation in tumor cell detection and chemotherapy response prediction. The developed algorithm is easily extensible to other tumor types and treatment modalities.
全球每年有 151900 人死于卵巢癌。治疗和预后主要取决于组织病理学解释结合分子诊断。然而,组织病理学模式与分子改变之间的关系尚未完全了解,并且很难使用已知的临床和组织学变量来预测患者的化疗反应。
我们分析了 587 例原发性浆液性卵巢腺癌患者的全切片组织病理学图像、RNA-Seq 和蛋白质组学数据,并开发了一种系统算法来整合组织病理学和功能组学发现,并预测患者对铂类化疗的反应。
我们的卷积神经网络识别出癌症区域的接收者操作特征曲线(AUCs)>0.95,肿瘤分级的 AUCs>0.80。功能组学分析显示,参与固有免疫反应和分解代谢途径的蛋白质表达水平与肿瘤分级相关。定量组织病理学分析成功地对不同铂类化疗反应的患者进行分层(P=0.003)。
这些结果表明定量组织病理学评估在肿瘤细胞检测和化疗反应预测方面具有潜在的临床应用价值。开发的算法易于扩展到其他肿瘤类型和治疗方式。