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应用血清拉曼光谱区分乳腺癌不同的HR状态OA

Differentiation of HR Status in Breast Cancer Using Serum Raman Spec-troscopy

中文摘要英文摘要

目的:开发使用血清样本的拉曼光谱技术,对乳腺癌患者激素受体(hormone receptor,HR)的针吸活检病理状态进行一致性评价.方法:采集 2021 年 7 月至 2023 年 5 月四川省肿瘤医院乳腺外科收治的 1 710 例浸润性乳腺癌患者肿瘤组织粗针穿刺活检(core needle biopsy,CNB)及外周静脉血标本,纳入首次就诊、临床信息齐全且人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)为阴性的患者,对CNB组织进行免疫组化染色和原位杂交,获得其分子分型病理结果,并对HR的状态进行标记.对外周静脉血样本进行预处理后采集血清的拉曼光谱,光谱数据经预处理后,按照 9:1 分为训练集和独立测试集,训练集使用t检验、Kruskal-Wallis U检验、Person和互信息分别进行特征提取,提取特征后使用Logistic回归(logistic regression,LR)、随机森林(random forest,RF)和支持向量机(support vector machine,SVM)对独立验证集的数据验证,并对不同方法得到的模型结果进行比较,对血清拉曼光谱对HR状态的病理标签一致性进行评价.结果:共计231 名患者纳入研究,HR+组134 例患者,平均年龄51.1 岁,HR-组 97 例患者,平均年龄 49.2 岁.通过t检验、Kruskal-Wallis U检验、Pearson和互信息提取特征后,分别使用LR、RF和SVM进行模型验证,最终结果AUC为0.71~0.90,特征提取方法方面t检验方法LR、RF、SVM分别为 0.85、0.83 和 0.86,Kruskal-Wallis U检验方法LR、RF、SVM分别为 0.89、0.84 和 0.90,Pearson方法LR、RF、SVM分别为 0.81、0.80 和 0.83,互信息方法LR、RF、SVM分别为 0.71、0.78 和 0.71,其中Kruskal-Wallis U检验筛选特征后使用SVM效果最好,AUC达0.9.但就一致性而言,使用LR进行模型验证的Kappa值较好,Kruskal-Wallis U检验方法结合LR可达 0.72.结论:来自于血清样本的拉曼光谱数据通过建模后与 CNB 结果有较好的吻合,其中Kruskal-Wallis U检验+SVM组合获得的AUC值最高,但结合Kappa值后Kruskal-Wallis U检验+LR的综合表现更好,具有进一步临床开发的潜力.

Objective:To develop a serum-based Raman spectroscopy technique to assess its concordance with core nee-dle biopsy(CNB)for determining hormone receptor(HR)status in breast cancer patients.Methods:A total of 1 710 pa-tients with invasive breast cancer were enrolled from the Department of Breast Surgery at Sichuan Cancer Hospital between Ju-ly 2021 and May 2023.Tumor tissue samples obtained via CNB and peripheral venous blood samples were collected from these patients.Patients who met the inclusion criteria[first diagnosis,complete clinical data,and human epidermal growth factor receptor 2(HER-2)-negative status]underwent CNB.Immunohistochemical staining and in situ hybridization were then performed on the biopsy specimens to determine the molecular subtype and HR status.After preprocessing the peripheral venous blood samples,serum was obtained for Raman spectroscopy acquisition.The resulting spectral data were then prepro-cessed and split into a training set(90%)and an independent test set(10%).Feature extraction was performed on the training set using the t-test,Kruskal-Wallis U test,Pearson correlation,and mutual information.The extracted features were used to build models with logistic regression(LR),random forest(RF)and support vector machine(SVM).These models were then validated on the independent test set.The results from the different modeling methods were compared to evaluate the concordance between the serum Raman spectra and the pathological HR status labels.Results:A total of 231 patients were enrolled in the study,with 134 patients in the HR+group(mean age:51.1 years)and 97 patients in the HR-group(mean age:49.2 years).Feature selection was performed using the t-test,Kruskal-Wallis U test,Pearson correlation,and mutual information.These selected features were then used to train and evaluate three classifiers:LR,RF,and SVM.The overall AUC values across all method-classifier combinations ranged from 0.71 to 0.90.The detailed performance is as fol-lows:t-test:LR=0.85,RF=0.83,SVM=0.86;Kruskal-Wallis U test:LR=0.89,RF=0.84,SVM=0.90;Pearson correlation:LR=0.81,RF=0.80,SVM=0.83;Mutual information:LR=0.71,RF=0.78,SVM=0.71.Among these,the combination of the Kruskal-Wallis U test and SVM achieved the highest AUC(0.90).However,when evaluated for classification consistency using the Kappa statistic,LR demonstrated superior performance(Kappa=0.72)when paired with the Kruskal-Wallis U test.Conclusion:Raman spectroscopy data from serum samples showed strong agreement with CNB results after modeling.Although the Kruskal-Wallis U test combined with SVM achieved the high-est AUC(0.90),the combination with LR demonstrated superior overall performance when both AUC and Kappa were con-sidered,highlighting its greater potential for clinical development.

李彦君;陈鳕姨;刘悦;杜雨杭;郭豪;李俊杰;张倩;王硕;李林涛

610041 成都,四川省肿瘤医院·研究所,放射肿瘤学四川省重点实验室,四川省肿瘤临床研究中心,四川省癌症防治中心,电子科技大学医学院附属肿瘤医院 放疗科610041 成都,四川省肿瘤医院·研究所,四川省肿瘤临床医学研究中心,四川省癌症防治中心,电子科技大学附属肿瘤医院 乳腺外科610041 成都,四川省肿瘤医院·研究所,放射肿瘤学四川省重点实验室,四川省肿瘤临床研究中心,四川省癌症防治中心,电子科技大学医学院附属肿瘤医院 放疗科610041 成都,四川省肿瘤医院·研究所,放射肿瘤学四川省重点实验室,四川省肿瘤临床研究中心,四川省癌症防治中心,电子科技大学医学院附属肿瘤医院 放疗科610041 成都,四川省肿瘤医院·研究所,放射肿瘤学四川省重点实验室,四川省肿瘤临床研究中心,四川省癌症防治中心,电子科技大学医学院附属肿瘤医院 放疗科610041 成都,四川省肿瘤医院·研究所,四川省肿瘤临床医学研究中心,四川省癌症防治中心,电子科技大学附属肿瘤医院 乳腺外科610041 成都,四川省肿瘤医院·研究所,四川省肿瘤临床医学研究中心,四川省癌症防治中心,电子科技大学附属肿瘤医院物资采购办公室610041 成都,四川省肿瘤医院·研究所,放射肿瘤学四川省重点实验室,四川省肿瘤临床研究中心,四川省癌症防治中心,电子科技大学医学院附属肿瘤医院 放疗科610041 成都,四川省肿瘤医院·研究所,放射肿瘤学四川省重点实验室,四川省肿瘤临床研究中心,四川省癌症防治中心,电子科技大学医学院附属肿瘤医院 放疗科

医药卫生

拉曼光谱人工智能乳腺癌激素受体液体活检

Raman spectroscopyArtificial intelligenceBreast cancerHormone receptorLiquid biopsy

《肿瘤预防与治疗》 2026 (1)

12-20,9

四川省医学会医学科研项目(编号:S20250023)成都市科技局技术创新研发项目(编号:2024-YF05-01955-SN) This study was supported by grants from Sichuan Medical Association(No.S20250023)and Chengdu Sci-ence and Technology Bureau(No.2024-YF05-01955-SN).

10.3969/j.issn.1674-0904.2026.01.003

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