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无监督机器学习模型利用放化疗开始前的白细胞计数揭示胶质母细胞瘤患者生存的预测标志物。

Unsupervised machine learning models reveal predictive markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

作者信息

Wang Wesley, Kumm Zeynep Temerit, Ho Cindy, Zanesco-Fontes Ideli, Texiera Gustavo, Reis Rui Manuel, Martinetto Horacio, Khan Javaria, Anderson Mark D, Chohan M Omar, Beyer Sasha, Elder J Brad, Giglio Pierre, Otero José Javier

机构信息

The Ohio State University Wexner Medical Center.

Barretos Cancer Hospital.

出版信息

Res Sq. 2023 Apr 21:rs.3.rs-2834239. doi: 10.21203/rs.3.rs-2834239/v1.

Abstract

PURPOSE

Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care.

METHODS

We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to nearly 600 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features.

RESULTS

We discovered that white blood cell count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of white blood cell count. By utilizing an objective PDL-1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PDL-1 expression in glioblastoma patients with high white blood cell counts.

CONCLUSION

These findings suggest that in a subset of glioblastoma patients the incorporation of white blood cell count and PDL-1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, use of machine learning models allows us to visualize complex clinical datasets to uncover novel clinical relationships.

摘要

目的

胶质母细胞瘤是一种恶性脑肿瘤,即使在进行初始治疗后仍需仔细的临床监测。个性化医疗建议使用各种分子生物标志物作为患者预后的预测指标或用于临床决策的因素。然而,这种分子检测的可及性对各机构构成了限制,这些机构需要识别低成本的预测性生物标志物以确保公平医疗。

方法

我们收集了俄亥俄州立大学、密西西比大学、巴雷托斯癌症医院(巴西)和弗莱尼研究所(阿根廷)诊治的胶质母细胞瘤患者的回顾性数据,共计近600份使用REDCap记录的患者病历。采用由降维和特征向量分析组成的无监督机器学习方法对患者进行评估,以可视化所收集临床特征之间的相互关系。

结果

我们发现,患者在基线治疗规划期间的白细胞计数可预测总体生存期,白细胞计数上四分位数和下四分位数之间的中位生存期差异超过6个月。通过使用客观的程序性死亡受体1(PDL-1)免疫组化定量算法,我们进一步能够确定白细胞计数高的胶质母细胞瘤患者中PDL-1表达增加。

结论

这些发现表明,在一部分胶质母细胞瘤患者中,将白细胞计数和脑肿瘤活检中的PDL-1表达纳入作为预测胶质母细胞瘤患者生存期的简单生物标志物。此外,使用机器学习模型使我们能够可视化复杂的临床数据集以发现新的临床关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9efa/10153371/3e6306f4be94/nihpp-rs2834239v1-f0001.jpg

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