PGC

PGC Full Name

progastricsin (pepsinogen C)

PGC Introduction

Pepsinogen C (PGC), also known as progastricsin, is an important aspartic protease secreted by the human gastric mucosa, serving as the inactive zymogen of its active form, pepsin C. In terms of origin and distribution, PGC differs from pepsinogen I (PGI). Although both are produced by gastric mucosal cells, PGC is secreted by a broader range of cell types. It is not only secreted by chief cells of the gastric fundic glands but is also widely present in the pyloric glands of the gastric antrum, cardiac glands, and Brunner's glands in the duodenum, whereas PGI is mainly confined to the gastric fundic glands. This widespread distribution enables serum PGC levels to more comprehensively reflect the health status of the entire gastric mucosa, including both the gastric body and antrum. Under physiological conditions, most of the secreted PGC enters the gastric lumen. In the acidic environment of the stomach, its molecular conformation changes, and an N‑terminal peptide segment is cleaved, activating it into the active enzyme pepsin C, which participates in the digestion of dietary proteins.

The core physiological function of PGC is to serve as a precursor of digestive enzymes. Once activated to pepsin C, it exerts strong proteolytic activity in the highly acidic gastric environment, breaking down large protein molecules into smaller peptides. This represents the first step in protein digestion, laying the groundwork for subsequent digestion and absorption in the small intestine. Because serum PGC levels are directly linked to the secretory function of the gastric mucosa, they are widely used to assess gastric mucosal health and pathological states. In clinical practice, PGC is typically measured not alone but in combination with PGI, and the PGI/PGC ratio (PGR) is calculated. This combined index, known as the "serum pepsinogen test" (PG method), has become an effective tool for screening high‑risk populations for gastric cancer, particularly patients with atrophic gastritis. When gastric mucosal atrophy occurs - especially when it predominantly affects the gastric body—the number of cells secreting PGI decreases significantly, leading to reduced serum levels of both PGI and the PGI/PGC ratio. Thus, low PGI levels and a low PGR are considered reliable markers of gastric mucosal atrophy, which is one of the most important precancerous conditions for gastric cancer.

Figure 1. Potential physiological functions of PGC. (Source: Shen S, et al. 2017)

Studies have shown that H. pylori infection can significantly influence the expression and secretion of PGC. In the early stages of H. pylori infection, the inflammatory response stimulates gastric mucosal cells, increasing the expression and secretion of PGC, which typically elevates serum PGC levels. This elevation reflects the active inflammatory state of the gastric mucosa. However, as H. pylori infection persists and becomes chronic, inflammation gradually damages the gastric glands, leading to glandular atrophy and intestinal metaplasia. During this process, the number of cells capable of secreting PGC gradually declines, and their function diminishes. Consequently, in advanced disease stages such as severe atrophic gastritis and gastric cancer, serum PGC levels tend to decrease. This dynamic pattern - from elevation to reduction - provides important clues for clinicians in staging disease and monitoring its progression.

Alternate Names for PGC

PGC; progastricsin (pepsinogen C); PEPC; PGII; gastricsin; pepsin C; pepsinogen C; preprogastricsin; pepsinogen group II;

• 1. Shen S, et al. Pepsinogen C expression, regulation and its relationship with cancer. Cancer Cell Int. 2017 May 23;17:57.
  2. Di Mario F, et al. Pepsinogen II in gastritis and Helicobacter pylori infection. Helicobacter. 2022 Apr;27(2):e12872.