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评估唾液中 CSTB 和 DMBT1 表达在胃癌患者和对照人群中的作用。

Evaluation of CSTB and DMBT1 expression in saliva of gastric cancer patients and controls.

机构信息

Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.

Department of Oral Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, North Kargar St, P.O.Box:14395-433, Tehran, 14399-55991, Iran.

出版信息

BMC Cancer. 2022 Apr 30;22(1):473. doi: 10.1186/s12885-022-09570-9.

Abstract

BACKGROUND

Gastric cancer (GC) is the fifth most common cancer and the third cause of cancer deaths globally, with late diagnosis, low survival rate, and poor prognosis. This case-control study aimed to evaluate the expression of cystatin B (CSTB) and deleted in malignant brain tumor 1 (DMBT1) in the saliva of GC patients with healthy individuals to construct diagnostic algorithms using statistical analysis and machine learning methods.

METHODS

Demographic data, clinical characteristics, and food intake habits of the case and control group were gathered through a standard checklist. Unstimulated whole saliva samples were taken from 31 healthy individuals and 31 GC patients. Through ELISA test and statistical analysis, the expression of salivary CSTB and DMBT1 proteins was evaluated. To construct diagnostic algorithms, we used the machine learning method.

RESULTS

The mean salivary expression of CSTB in GC patients was significantly lower (115.55 ± 7.06, p = 0.001), and the mean salivary expression of DMBT1 in GC patients was significantly higher (171.88 ± 39.67, p = 0.002) than the control. Multiple linear regression analysis demonstrated that GC was significantly correlated with high levels of DMBT1 after controlling the effects of age of participants (R = 0.20, p < 0.001). Considering salivary CSTB greater than 119.06 ng/mL as an optimal cut-off value, the sensitivity and specificity of CSTB in the diagnosis of GC were 83.87 and 70.97%, respectively. The area under the ROC curve was calculated as 0.728. The optimal cut-off value of DMBT1 for differentiating GC patients from controls was greater than 146.33 ng/mL (sensitivity = 80.65% and specificity = 64.52%). The area under the ROC curve was up to 0.741. As a result of the machine learning method, the area under the receiver-operating characteristic curve for the diagnostic ability of CSTB, DMBT1, demographic data, clinical characteristics, and food intake habits was 0.95. The machine learning model's sensitivity, specificity, and accuracy were 100, 70.8, and 80.5%, respectively.

CONCLUSION

Salivary levels of DMBT1 and CSTB may be accurate in diagnosing GCs. Machine learning analyses using salivary biomarkers, demographic, clinical, and nutrition habits data simultaneously could provide affordability models with acceptable accuracy for differentiation of GC by a cost-effective and non-invasive method.

摘要

背景

胃癌(GC)是全球第五大常见癌症和第三大癌症死亡原因,其诊断较晚,生存率低,预后差。本病例对照研究旨在评估胱抑素 B(CSTB)和恶性脑肿瘤缺失 1 蛋白(DMBT1)在 GC 患者唾液中的表达,并用统计分析和机器学习方法构建诊断算法。

方法

通过标准检查表收集病例组和对照组的人口统计学数据、临床特征和饮食摄入习惯。从 31 名健康个体和 31 名 GC 患者中采集未刺激的全唾液样本。通过 ELISA 检测和统计分析评估唾液 CSTB 和 DMBT1 蛋白的表达。为了构建诊断算法,我们使用了机器学习方法。

结果

GC 患者唾液 CSTB 的平均表达明显降低(115.55±7.06,p=0.001),GC 患者唾液 DMBT1 的平均表达明显升高(171.88±39.67,p=0.002)。多元线性回归分析表明,在控制参与者年龄影响后,GC 与高水平的 DMBT1 显著相关(R=0.20,p<0.001)。考虑到 CSTB 大于 119.06ng/mL 作为最佳截断值,CSTB 在 GC 诊断中的敏感性和特异性分别为 83.87%和 70.97%。ROC 曲线下面积计算为 0.728。用于区分 GC 患者和对照组的 DMBT1 的最佳截断值大于 146.33ng/mL(敏感性=80.65%和特异性=64.52%)。ROC 曲线下面积高达 0.741。通过机器学习方法,CSTB、DMBT1、人口统计学数据、临床特征和饮食摄入习惯的诊断能力的 ROC 曲线下面积为 0.95。机器学习模型的敏感性、特异性和准确性分别为 100%、70.8%和 80.5%。

结论

唾液中的 DMBT1 和 CSTB 水平可能是 GC 诊断的准确指标。使用唾液生物标志物、人口统计学、临床和营养习惯数据的机器学习分析,同时可以提供具有可接受准确性的经济实惠模型,通过经济有效的非侵入性方法来区分 GC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2a9/9055774/dad8309d3e3d/12885_2022_9570_Fig1_HTML.jpg

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