Pepsinogen C expression, regulation and its relationship with cancer

Pepsinogen C (PGC) belongs to the aspartic protease family and is secreted by gastric chief cells. PGC could be activated to pepsin C and digests polypeptides and amino acids, but as a zymogen PGC’s functions is unclear. In normal physiological conditions, PGC is initially detected in the late embryonic stage and is mainly expressed in gastric mucosa. The in situ expression of PGC in gastric mucosa is decreased considerably in the process of superficial gastritis → atrophic gastritis → gastric cancer (GC), proving that PGC is a comparatively ideal negative marker of GC. Serum PGC, and PGA levels and the PGA/PGC ratio have satisfactory sensitivity, specificity and price–quality ratio for predicting high GC risk. Ectopic PGC expression is significantly increased in prostate cancer, breast cancer, ovary cancer and endometrial cancer. In those sex-related cancers high level PGC expression indicates better prognosis and longer survival. The regulation of PGC expression involves genetic and epigenetic alteration of the encoding PGC gene, hormones modulation and interactions between PGC with other transcription factors and protein kinases. More and more research evidence hinted that PGC has strong correlation with cancer. In the systematic review, we respectively elaborate the structure, potential physiological functions, expression characteristics and regulation of PGC, and especially focus on the relationship between PGC expression and cancer to highlight the role of PGC in the tumorigenesis and its application value in clinical practice.