Pepsinogen C expression, regulation and its relationship with cancer

Abstract

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.

Correlation between negative expression of pepsinogen C and a series of phenotypic markers of gastric cancer in different gastric diseases

“…Our previous results also indicated that the expression level of PGC gradually declined during SG‐AG‐GC progression 13. Melle et al14 also found that PGC was obviously reduced in gastric cancer tissue by ProteinChip Arrays and SELDI‐TOF MS. As a negative marker, PGC has demonstrated important value in the screening, diagnosis, and prognosis of gastric cancer 15, 16…”

Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells

“…3d). Notably, the IM + CK organoids had significantly lower levels of SATB2 20 , Albumin (ALB), and Pepsinogen C (PGC) 39 expression compared with the CK + DCI HIOs (and IM + CHIR), suggesting that the IM + CK condition results in HIOs that are more homogenous and express markers specific to intestinal lineages, while preventing the emergence of hepatic and gastric lineages (Supplementary Fig. 3).…”

In Vivo Removal of N-Terminal Fusion Domains From Recombinant Target Proteins Produced in Nicotiana benthamiana

“…The advantage of this approach is that many different foreign domains may be fused to a target protein to increase its expression level or solubility and then be removed after expression in vivo, thereby allowing production of a target protein without any extra foreign domains. This strategy has been widely used for the production of many endogenous proteins, including growth factors and cytokines in animal cells as well as proteases such as pepsin and trypsin (Shi et al, 2011;Kim et al, 2011;Shen et al, 2017). These proteins are expressed as preproproteins and then converted to their functional form via proteolytic processing.…”