Salivary function impairment in type 2 Diabetes patients associated with concentration and genetic polymorphisms of chromogranin A.

OBJECTIVES: The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. MATERIALS AND METHODS: Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P < 0.001, respectively). CHGA gene variants (T-415C and Glu264Asp) revealed significant differences between diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P < 0.05). CONCLUSIONS: T2DM causes abnormalities in the function of salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. CLINICAL RELEVANCE: Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. This could be a significant insight to establish a role for salivary CHGA as a potential clinical biomarker to T2DM.

Three Molecular Subtypes of Gastric Adenocarcinoma Have Distinct Histochemical Features Reflecting Epstein-Barr Virus Infection Status and Neuroendocrine Differentiation.

Current histopathologic classification schemes for gastric adenocarcinoma have limited clinical utility and are difficult to apply due to tumor heterogeneity. Elucidation of molecular subtypes of gastric cancer may contribute to our understanding of gastric cancer biology and to the development of new molecular markers that may lead to improved diagnosis, therapy, or prognosis. We previously demonstrated that Epstein-Barr virus (EBV)-infected gastric cancers have a distinct human gene expression profile compared with uninfected cancers. We now examine the histopathologic features characterizing infected (n=14) and uninfected (n=89) cancers; the latter of which are now further divided into 2 major molecular subtypes based on expression patterns of 93 RNAs. One uninfected gastric cancer subtype was distinguished by upregulation of 3 genes with neuroendocrine (NE) function (CHGA, GAST, and REG4 encoding chromogranin, gastrin, and the secreted peptide REG4 involved in epithelial cell regeneration), implicating hormonal factors in the pathogenesis of a major class of gastric adenocarcinomas. Evidence of NE differentiation (molecular, immunohistochemical, or morphologic) was mutually exclusive of EBV infection. EBV-infected tumors tended to have solid-type morphology with lymphoid stroma. This study reveals novel molecular subtypes of gastric cancer and their associated morphologies that demonstrate divergent NE features.