{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPepsinogen C (PGC) is a secreted aspartic protease predominantly expressed by differentiated gastric epithelial cells where it serves as a sensitive molecular marker of mature mucosa. A number of clinical studies have demonstrated that quantitative changes in PGC expression—as measured in serum or tissue—correlate with precancerous conditions and gastric cancer risk. In particular, reduced or aberrant PGC levels have been associated with atrophic chronic gastritis and the subsequent progression to malignancy, while favorable PGC gene variants tend to up‐regulate its expression and sustain gastric differentiation. These observations support the use of PGC, either alone or in combination with other serum pepsinogens, as a noninvasive biomarker for detecting early gastric lesions and stratifying cancer risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role as a clinical biomarker, genetic and functional studies have revealed that variations in the PGC gene—as well as its integration into complex regulatory networks—influence individual susceptibility to H. pylori–associated gastritis and gastric cancer. Specific insertion/deletion polymorphisms and single‐nucleotide variants in PGC, together with their interactions with host genes and noncoding RNAs, have been shown to modulate PGC promoter activity, mRNA levels, and protein expression. These genetic interactions, involving loci such as IL1B and PTPN11 and networks revealed by competing endogenous RNA analyses, underscore the importance of PGC regulation in the pathogenesis of gastric lesions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its established role in the stomach, PGC expression has also been documented in extragastric tissues. For instance, in pulmonary alveolar type 2 cells PGC contributes to the proteolytic processing of pro–surfactant protein B, a critical step in the maturation of pulmonary surfactant. Moreover, in tumors of non‐gastric origin—such as certain breast cancers and uveal melanomas—PGC expression has been linked to favorable prognoses, suggesting that its function as a differentiation marker may extend to other tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hui-Jie Liu, Xiao-Lin Guo, Ming Dong, et al. 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