Salivary proteomics of patients with type 2 diabetes identify potential biomarkers for diabetes and highlight significant role of immune response

Diabetes is a global public health problem, causing diverse complications, consequently compromising patient quality of life. Salivary proteome is affected by pathological conditions, however, the contributions of salivary proteins to diabetes are not fully understood. Hence, this study aimed to evaluate the changes of salivary proteomes in patients with diabetes through LC-MS/MS technology. Proteomics analysis identified 1186 differently expressed proteins (DEPs) in saliva from patients with diabetes versus normal control, among which 851 were upregulated and 335 were downregulated. Functional analysis highlighted the enrichments in immune response and immune response-related signaling pathways. Further comparative analysis between mild and severe diabetes identified 386 DEPs including 262 upregulated and 124 downregulated. Functional annotation enriched significantly in immune response and calcium signaling pathway. By K-means and weighted gene co-expression network analysis, five candidate proteins were selected for further verification. Notably, ELISA and correlation analysis discovered that CAMK2D was increased in the diabetic saliva in a stage-dependent manner, and salivary CAMK2D content was positively correlated to blood glucose and glycosylated hemoglobin; while SPRR2A was decreased, and negatively correlated to blood glucose and glycosylated hemoglobin. Therefore, CAMK2D and SPRR2A may participate in the pathology and aggravation of diabetes by regulating immune response through calcium signaling pathway, and may serve as potential salivary biomarkers and therapeutic targets for diabetes.