Salivary Glycopatterns as Potential Biomarkers for Screening of Early-Stage Breast Cancer

Abstract

Objective

We systematically investigated and assessed the alterations of salivary glycopatterns and possibility as biomarkers for diagnosis of early-stage breast cancer.

Design

Alterations of salivary glycopatterns were probed using lectin microarrays and blotting analysis from 337 patients with breast benign cyst or tumor (BB) or breast cancer (I/II stage) and 110 healthy humans. Their diagnostic models were constructed by a logistic stepwise regression in the retrospective cohort. Then, the performance of the diagnostic models were assessed by ROC analysis in the validation cohort. Finally, a double-blind cohort was tested to confirm the application potential of the diagnostic models.

Results

The diagnostic models were constructed based on 9 candidate lectins (e.g., PHA-E + L, BS-I, and NPA) that exhibited significant alterations of salivary glycopatterns, which achieved better diagnostic powers with an AUC value > 0.750 (p < 0.001) for the diagnosis of BB (AUC: 0.752, sensitivity: 0.600, and specificity: 0.835) and I stage breast cancer (AUC: 0.755, sensitivity: 0.733, and specificity: 0.742) in the validation cohort. The diagnostic model of I stage breast cancer exhibited a high accuracy of 0.902 in double-blind cohort.

Conclusions

This study could contribute to the screening for patients with early-stage breast cancer based on precise alterations of salivary glycopatterns.

Highlights

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  This first-in-humansaliva experience demonstrated that alterations of salivary glycopatterns arerelated to breast disease.

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  The constructivediagnostic model achieved better diagnostic powers for the diagnosis of I stagebreast cancer.

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  It could be asbiomarkers for the screening of patients with early-stage breast cancer.

Salivary diagnostic strategy now exhibits advantages of easy access, precise, non-invasive collection and dynamic monitoring. Breast cancer is one of the commonly diagnosed malignancies worldwide, threatening to female health seriously. Because glycoprotein glycans play an important role in the pathogenesis and progression of various diseases. This present study focuses on the changes in the glycan structures of salivary proteins related to breast disease, and could encourage researchers to consider the use of saliva to follow the development of patients with breast cancer at an early stage by monitoring the expressive changes of certain glycans.