progastrinreleasing

Progastrin‑releasing peptide (ProGRP) is an 31‑amino‑acid prohormone that is processed to generate activity in the nervous and gastrointestinal systems. It is a member of the gastrin‑releasing peptide family and is synthesized primarily by neuroendocrine cells throughout the body. The precursor is cleaved by prohormone convertases, producing the mature neuropeptide gastrin‑releasing peptide (GRP), which is a potent mitogen for gastric mucosa and modulates sensory signaling.

In addition to its physiological roles, ProGRP is used as a biomarker for neuroendocrine tumours, most notably small‑cell lung carcinoma (SCLC). Serum levels of ProGRP rise sharply in patients with SCLC and correlate with tumour burden. Consequently, ProGRP is employed in clinical diagnostics to differentiate SCLC from non‑small cell lung cancers, to monitor treatment response, and to detect recurrence. Elevated ProGRP may also occur in other neuroendocrine tumours, such as medullary thyroid carcinoma and pancreatic neuroendocrine tumors, though its specificity is highest for SCLC.

The gene encoding ProGRP, known as CHGA or preprogastrin‑releasing granule protein, is located on chromosome 19q13 and contains regulatory elements that respond to catecholamine signals and hypoxic conditions. Genetic polymorphisms in this locus have been explored for associations with tumour aggressiveness and patient prognosis.

Research has investigated the signaling pathways downstream of GRP receptor activation, including the phospholipase C/inositol triphosphate cascade, JAK/STAT, and MAPK/ERK pathways. These pathways mediate cell proliferation, survival, and angiogenesis, contributing to the malignant phenotype of neuroendocrine tumours.

Overall, ProGRP is a clinically relevant peptide that functions as both a biological mediator in the nervous system and a diagnostic marker for certain cancers. Its measurement in serum plasma provides a minimally invasive tool for clinicians managing patients with suspected neuroendocrine malignancies.