Exploring the role of progastricsin/pepsinogen-c (PGC) in gastric carcinogenesis: A South Asian outlook.

Abstract

e16024 Background: Progastricsin/Pepsinogen C (PGC) is an endo-protease expressed by gastric fundic cells, glandular cells, chief cells as well as by extra gastric organs including prostate, seminal vesical, breast and lungs. Upregulation of PGC expression has been reported in cancers of liver, pancreas, breast, ovaries, endometrium and skin. However, sequential downregulation of PGC has been reported in advancing stages of gastric inflammation through to gastric carcinoma. In this study, we investigated PGC expression profile in stomach adenocarcinoma (STAD) patients from Pakistan. Data on PGC expression in South Asian patients are scarce and therefore our study holds potential to contribute towards understanding the role of PGC in gastric carcinogenesis in our genetically, diet-wise and environmentally distinct population. Methods: In order to investigate expression profile of PGC in STAD, tissues biopsied from patients clinically suspected for STAD were snap frozen. Samples were further processed only upon histopathological confirmation of STAD diagnosis (n = 18). Tissues were processed for nucleic acid extraction, cDNA synthesis and qPCR using SYBR Green chemistry. In order to quantify relative fold change in PGC expression in STAD, normal gastric tissues positive (n = 10) and negative (n = 8) for H.pylori infection were used as controls. All samples were run in duplicates and average CT values were used for further analyses. Relative quantification was performed using the 2 -∆∆CT values. Results: In our cohort of STAD patients, mean age at presentation was 52.7Y with minimum and maximum ages being 34Y and 72Y respectively. 27.8% (n = 5) of our patients were females while 72.2% (n = 13) were males. All recruited patients were diagnosed with STAD on hisopathological examination and none of them received prior radiotherapy and/or chemotherapy. 22.2% (n = 4) patients presented with distant metastasis to liver (n = 2), lungs (n = 1) and mesentery (n = 1). All STAD patients in our study were negative for H.pylori infection. PGC expression was downregulated in all STAD tissues compared to normal stomach tissue regardless of the H.pylori infection status of controls. However, PGC downregulation was significantly higher in STAD tissues when compared to H.pylori negative controls versus the H.pylori positive controls. Conclusions: We report PGC downregulation in STAD patients from Pakistan. To the best of our knowledge, this is the first study investigating PGC expression profile in South Asian STAD patients and therefore our findings are relevant in understanding gastric carcinogenesis as well to identify molecules of diagnostic, therapeutic and prognostic significance in our population.