Expression of pepsinogen A (PGA/PG I) in breast cancer and non-cancer tissues and its relationship with clinicopathological parameters of breast cancer

Abstract Background Human pepsinogens (PGs) are inactive pro-enzymes for the specific digestive enzyme--pepsin originating from the gastric mucosa, Pepsinogens A (PGA) is one of pepsinogens family members. In the past, relevant studies in PGA mainly focused on gastric diseases, but there were few reports outside the stomach. Further understanding of the relationship between PGA and extra-gastric diseases, especially cancer, is helpful to fully understand the role and function of PGA. Methods Total of 362 patients with different breast disease after surgery were registered in the study. Immunohistochemical staining was used for PGA expression. GEO, and a series of software packages based on R language were used for further validation as well as function analysis of PGA in breast cancer. Results There were significant statistical differences of PGA expression between breast cancer and non-cancer tissues including different benign breast diseases. The results of correlation between PGA expression and clinicopathological parameters of breast cancer showed that there was no significant correlation between PGA expression and general clinicopathological parameters except molecular classification of breast cancer. Analysis with GEO showed that higher PGA expression may indicate a poor prognosis of breast cancer. GO and KEGG analysis showed that PGA may be involved in PPAR signaling pathway and AMPK signaling pathway regulation mechanisms. Conclusions The expression of PGA in breast cancer was significantly higher than that of non-cancer tissues, and it was related to molecular classification of breast cancer. the prognosis of patients with higher PGA mRNA expression was poorer. PGA may function through interactions with PPAR signaling pathway and AMPK signaling pathway in breast cancer.