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基于人工智能的乳腺Ki67定量免疫组织化学分析

Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence.

作者信息

Wang Wenhui, Gong Yitang, Chen Bingxian, Guo Hualei, Wang Qiang, Li Jing, Jin Cheng, Gui Kun, Chen Hao

机构信息

Department of Pathology, Hangzhou Women's Hospital, Hangzhou, 310008, Zhejiang, China.

Ningbo Konfoong Bioinformation Tech Co., Ltd, Ningbo, China.

出版信息

Open Life Sci. 2024 Dec 31;19(1):20221013. doi: 10.1515/biol-2022-1013. eCollection 2024.

Abstract

Breast cancer is a common malignant tumor of women. Ki67 is an important biomarker of cell proliferation. With the quantitative analysis, it is an important indicator of malignancy for breast cancer diagnosis. However, it is difficult to accurately and quantitatively evaluate the count of positive nucleus during the diagnosis process of pathologists, and the process is time-consuming and labor-intensive. In this work, we employed a quantitative analysis method of Ki67 in breast cancer based on deep learning approach. For the diagnosis of breast cancer, according to breast cancer diagnosis guideline, we first identified the tumor region of Ki67 pathological image, neglecting the non-tumor region in the image. Then, we detect the nucleus in the tumor region to determine the nucleus location information. After that, we classify the detected nucleuses as positive and negative according to the expression level of Ki67. According to the results of quantitative analysis, the proportion of positive cells is counted. Combining the above process, we design a breast Ki67 quantitative analysis pipeline. The Ki67 quantitative analysis system was assessed on the validation set. The Dice coefficient of the tumor region segmentation model was 0.848, the Average Precision index of the nucleus detection model was 0.817, and the accuracy of the nucleus classification model was 96.66%. Besides, in clinical independent sample experiment, the results show that the proposed breast Ki67 quantitative analysis system achieve excellent correlation with the diagnosis efficiency of doctors improved more than ten times and the overall consistency of diagnosis is intra-group correlation coefficient: 0.964. The research indicates that our quantitative analysis method of Ki67 in breast cancer has high clinical application value.

摘要

乳腺癌是女性常见的恶性肿瘤。Ki67是细胞增殖的重要生物标志物。通过定量分析,它是乳腺癌诊断中恶性程度的重要指标。然而,在病理学家的诊断过程中,难以准确且定量地评估阳性细胞核的数量,并且该过程耗时且费力。在这项工作中,我们采用了基于深度学习方法的乳腺癌Ki67定量分析方法。对于乳腺癌的诊断,根据乳腺癌诊断指南,我们首先识别Ki67病理图像的肿瘤区域,忽略图像中的非肿瘤区域。然后,我们在肿瘤区域检测细胞核以确定细胞核的位置信息。之后,根据Ki67的表达水平将检测到的细胞核分类为阳性和阴性。根据定量分析结果,计算阳性细胞的比例。结合上述过程,我们设计了一个乳腺Ki67定量分析流程。在验证集上对Ki67定量分析系统进行了评估。肿瘤区域分割模型的Dice系数为0.848,细胞核检测模型的平均精度指数为0.817,细胞核分类模型的准确率为96.66%。此外,在临床独立样本实验中,结果表明所提出的乳腺Ki67定量分析系统与医生的诊断效率具有极好的相关性,提高了十多倍,诊断的总体一致性为组内相关系数:0.964。研究表明,我们的乳腺癌Ki67定量分析方法具有较高的临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7e7/11751672/ef0b26809ac9/j_biol-2022-1013-fig001.jpg

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