Endocrine Abstracts

Purpose

There is a continuity of changes ranging from enterochromaffin‐like (ECL) cell hyperplasia to type 1 gastric neuroendocrine neoplasms (GNEN1) with important clinical implications. Although the effect of the circadian clock system on tumorigenesis has been addressed, the role of the peripheral clock system in the transition from ECL-cell hyperplasia to GNEN1 remains to be explored.

Methods

Six patients diagnosed with GNEN1 and 10 patients with ECL-cell hyperplasia were included. Blood samples were collected at 0800 h, 1500 h and 2000 h for peripheral blood mononuclear cells (PBMCs) isolation. The mRNA expression of Clock-related genes (CLOCK, BMAL1, CRY-1, PER-2 ROR-α and REV-ERBbeta) were evaluated by real-time quantitative PCR from PBMCs.

Results

In patients with GNEN1, BMAL genes where lower expressed at night than early in the morning (P = 0.02), whereas patients with ECL-cell hyperplasia expressed lower transcript levels of PER2 and REV-ERB beta at these time points (P = 0.03, P = 0.05, respectively). In addition, patients with GNEN1 expressed lower transcript levels of CLOCK, PER2 and REV-ERB beta in the early evening than in the morning (P = 0.04; P = 0.03; P = 0.05, respectively). When comparing the two groups (GNEN1 vs ECL-cell hyperplasia) at the three different time points, we confirmed a marginal increase in CLOCK, PER2 and REV-ERB beta expression early in the morning (P = 0.06, 0.02 and 0.07, respectively); a marginal increase in REV-ERB beta expression in the early evening (P = 0.09) and a marginal increase in BMAL at night (P = 0.09) in patients with GNEN1.

Conclucions

Our findings point towards an uregulated expression of Clock-related genes in patients with GNEN1 as compared to EC-cellL hyperplasia, suggesting a possible involvement in GNEN1 tumorigenesis.