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Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Review

Pepsinogen C expression, regulation and its relationship with cancer

Authors: Shixuan Shen, Jingyi Jiang, Yuan Yuan

Published in: Cancer Cell International | Issue 1/2017

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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.
Literature
1.
go back to reference Hassan MI, Toor A, Ahmad F. Progastriscin: structure, function, and its role in tumor progression. J Mol Cell Biol. 2010;2(3):118–27.CrossRefPubMed Hassan MI, Toor A, Ahmad F. Progastriscin: structure, function, and its role in tumor progression. J Mol Cell Biol. 2010;2(3):118–27.CrossRefPubMed
2.
go back to reference Diaz M, Rodriguez JC, Sanchez J, Sanchez MT, Martin A, Merino AM, Vizoso F. Clinical significance of pepsinogen C tumor expression in patients with stage D2 prostate carcinoma. Int J Biol Mark. 2002;17(2):125–9.CrossRef Diaz M, Rodriguez JC, Sanchez J, Sanchez MT, Martin A, Merino AM, Vizoso F. Clinical significance of pepsinogen C tumor expression in patients with stage D2 prostate carcinoma. Int J Biol Mark. 2002;17(2):125–9.CrossRef
3.
go back to reference Foster C, Aktar A, Kopf D, Zhang P, Guttentag S. Pepsinogen C: a type 2 cell-specific protease. Am J Physiol Lung Cell Mol Physiol. 2004;286(2):L382–7.CrossRefPubMed Foster C, Aktar A, Kopf D, Zhang P, Guttentag S. Pepsinogen C: a type 2 cell-specific protease. Am J Physiol Lung Cell Mol Physiol. 2004;286(2):L382–7.CrossRefPubMed
4.
go back to reference Reid WA, Vongsorasak L, Svasti J, Valler MJ, Kay J. Identification of the acid proteinase in human seminal fluid as a gastricsin originating in the prostate. Cell Tissue Res. 1984;236(3):597–600.CrossRefPubMed Reid WA, Vongsorasak L, Svasti J, Valler MJ, Kay J. Identification of the acid proteinase in human seminal fluid as a gastricsin originating in the prostate. Cell Tissue Res. 1984;236(3):597–600.CrossRefPubMed
5.
go back to reference Antunes AA, Reis ST, Leite KR, Real DM, Sousa-Canavez JM, Camara-Lopes LH, Dall’Oglio MF, Srougi M. PGC and PSMA in prostate cancer diagnosis: tissue analysis from biopsy samples. Int Braz J Urol Off J Braz Soc Urol. 2013;39(5):649–56.CrossRef Antunes AA, Reis ST, Leite KR, Real DM, Sousa-Canavez JM, Camara-Lopes LH, Dall’Oglio MF, Srougi M. PGC and PSMA in prostate cancer diagnosis: tissue analysis from biopsy samples. Int Braz J Urol Off J Braz Soc Urol. 2013;39(5):649–56.CrossRef
6.
go back to reference Serra C, Vizoso F, Lamelas ML, Rodriguez JC, Gonzalez LO, Merino AM, Baltasar A, Perez-Vazquez MT, Medrano J. Comparative study of two androgen-induced markers (apolipoprotein D and pepsinogen C) in female and male breast carcinoma. Int J Surg Invest. 2000;2(3):183–92. Serra C, Vizoso F, Lamelas ML, Rodriguez JC, Gonzalez LO, Merino AM, Baltasar A, Perez-Vazquez MT, Medrano J. Comparative study of two androgen-induced markers (apolipoprotein D and pepsinogen C) in female and male breast carcinoma. Int J Surg Invest. 2000;2(3):183–92.
7.
go back to reference Serra Diaz C, Vizoso F, Rodriguez JC, Merino AM, Gonzalez LO, Baltasar A, Perez-Vazquez MT, Medrano J. Expression of pepsinogen C in gynecomastias and male breast carcinomas. World J Surg. 1999;23(5):439–45.CrossRefPubMed Serra Diaz C, Vizoso F, Rodriguez JC, Merino AM, Gonzalez LO, Baltasar A, Perez-Vazquez MT, Medrano J. Expression of pepsinogen C in gynecomastias and male breast carcinomas. World J Surg. 1999;23(5):439–45.CrossRefPubMed
8.
go back to reference Rojo JV, Merino AM, Gonzalez LO, Vizoso F. Expression and clinical significance of pepsinogen C in epithelial ovarian carcinomas. Eur J Obstet Gynecol Reprod Biol. 2002;104(1):58–63.CrossRefPubMed Rojo JV, Merino AM, Gonzalez LO, Vizoso F. Expression and clinical significance of pepsinogen C in epithelial ovarian carcinomas. Eur J Obstet Gynecol Reprod Biol. 2002;104(1):58–63.CrossRefPubMed
9.
go back to reference Kageyama T. Pepsinogens, progastricsins, and prochymosins: structure, function, evolution, and development. Cell Mol Life Sci. 2002;59(2):288–306.CrossRefPubMed Kageyama T. Pepsinogens, progastricsins, and prochymosins: structure, function, evolution, and development. Cell Mol Life Sci. 2002;59(2):288–306.CrossRefPubMed
10.
go back to reference Richter C, Tanaka T, Yada RY. Mechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin. Biochem J. 1998;335(Pt 3):481–90.CrossRefPubMedPubMedCentral Richter C, Tanaka T, Yada RY. Mechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin. Biochem J. 1998;335(Pt 3):481–90.CrossRefPubMedPubMedCentral
11.
go back to reference Yoshimasu MA, Tanaka T, Ahn JK, Yada RY. Effect of N-linked glycosylation on the aspartic proteinase porcine pepsin expressed from Pichia pastoris. Glycobiology. 2004;14(5):417–29.CrossRefPubMed Yoshimasu MA, Tanaka T, Ahn JK, Yada RY. Effect of N-linked glycosylation on the aspartic proteinase porcine pepsin expressed from Pichia pastoris. Glycobiology. 2004;14(5):417–29.CrossRefPubMed
12.
go back to reference Elabiad MT, Zhang J. Detection of pepsinogen in the neonatal lung and stomach by immunohistochemistry. J Pediatric Gastroenterol Nutr. 2011;53(4):401–3.CrossRef Elabiad MT, Zhang J. Detection of pepsinogen in the neonatal lung and stomach by immunohistochemistry. J Pediatric Gastroenterol Nutr. 2011;53(4):401–3.CrossRef
13.
go back to reference Feng S, Li W, Lin H. Characterization and expression of the pepsinogen C gene and determination of pepsin-like enzyme activity from orange-spotted grouper (Epinephelus coioides). Comp Biochem Physiol B: Biochem Mol Biol. 2008;149(2):275–84.CrossRef Feng S, Li W, Lin H. Characterization and expression of the pepsinogen C gene and determination of pepsin-like enzyme activity from orange-spotted grouper (Epinephelus coioides). Comp Biochem Physiol B: Biochem Mol Biol. 2008;149(2):275–84.CrossRef
14.
go back to reference Fukuda K, Ishii Y, Saiga H, Shiokawa K, Yasugi S. Mesenchymal regulation of epithelial gene expression in developing avian stomach: 5′-flanking region of pepsinogen gene can mediate mesenchymal influence on its expression. Development. 1994;120(12):3487–95.PubMed Fukuda K, Ishii Y, Saiga H, Shiokawa K, Yasugi S. Mesenchymal regulation of epithelial gene expression in developing avian stomach: 5′-flanking region of pepsinogen gene can mediate mesenchymal influence on its expression. Development. 1994;120(12):3487–95.PubMed
15.
go back to reference Kishi K, Kinoshita Y, Matsushima Y, Okada A, Maekawa T, Kawanami C, Watanabe N, Chiba T. Pepsinogen C gene product is a possible growth factor during gastric mucosal healing. Biochem Biophys Res Commun. 1997;238(1):17–20.CrossRefPubMed Kishi K, Kinoshita Y, Matsushima Y, Okada A, Maekawa T, Kawanami C, Watanabe N, Chiba T. Pepsinogen C gene product is a possible growth factor during gastric mucosal healing. Biochem Biophys Res Commun. 1997;238(1):17–20.CrossRefPubMed
16.
go back to reference Minn I, Kim HS, Kim SC. Antimicrobial peptides derived from pepsinogens in the stomach of the bullfrog, Rana catesbeiana. Biochem Biophys Acta. 1998;1407(1):31–9.PubMed Minn I, Kim HS, Kim SC. Antimicrobial peptides derived from pepsinogens in the stomach of the bullfrog, Rana catesbeiana. Biochem Biophys Acta. 1998;1407(1):31–9.PubMed
17.
go back to reference Gerson KD, Foster CD, Zhang P, Zhang Z, Rosenblatt MM, Guttentag SH. Pepsinogen C proteolytic processing of surfactant protein B. J Biol Chem. 2008;283(16):10330–8.CrossRefPubMedPubMedCentral Gerson KD, Foster CD, Zhang P, Zhang Z, Rosenblatt MM, Guttentag SH. Pepsinogen C proteolytic processing of surfactant protein B. J Biol Chem. 2008;283(16):10330–8.CrossRefPubMedPubMedCentral
18.
go back to reference Sorensen OE, Gram L, Johnsen AH, Andersson E, Bangsboll S, Tjabringa GS, Hiemstra PS, Malm J, Egesten A, Borregaard N. Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. J Biol Chem. 2003;278(31):28540–6.CrossRefPubMed Sorensen OE, Gram L, Johnsen AH, Andersson E, Bangsboll S, Tjabringa GS, Hiemstra PS, Malm J, Egesten A, Borregaard N. Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. J Biol Chem. 2003;278(31):28540–6.CrossRefPubMed
19.
go back to reference Szecsi PB, Lilja H. Gastricsin-mediated proteolytic degradation of human seminal fluid proteins at pH levels found in the human vagina. J Androl. 1993;14(5):351–8.PubMed Szecsi PB, Lilja H. Gastricsin-mediated proteolytic degradation of human seminal fluid proteins at pH levels found in the human vagina. J Androl. 1993;14(5):351–8.PubMed
20.
go back to reference Dos Reis ST, Pontes J Jr, Villanova FE, Borra PM, Antunes AA, Dall’oglio MF, Srougi M, Leite KR. Genetic polymorphisms of matrix metalloproteinases: susceptibility and prognostic implications for prostate cancer. J Urol. 2009;181(5):2320–5.CrossRefPubMed Dos Reis ST, Pontes J Jr, Villanova FE, Borra PM, Antunes AA, Dall’oglio MF, Srougi M, Leite KR. Genetic polymorphisms of matrix metalloproteinases: susceptibility and prognostic implications for prostate cancer. J Urol. 2009;181(5):2320–5.CrossRefPubMed
21.
go back to reference Ning PF, Sun LP, Liu HJ, Yuan Y. Expression of pepsinogen C in gastric cancer and its precursor. Zhonghua yi xue za zhi. 2004;84(10):818–21.PubMed Ning PF, Sun LP, Liu HJ, Yuan Y. Expression of pepsinogen C in gastric cancer and its precursor. Zhonghua yi xue za zhi. 2004;84(10):818–21.PubMed
22.
go back to reference Ning PF, Liu HJ, Yuan Y. Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and Helicobacter pylori associated gastric diseases. World J Gastroenterol. 2005;11(17):2545–8.CrossRefPubMedPubMedCentral Ning PF, Liu HJ, Yuan Y. Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and Helicobacter pylori associated gastric diseases. World J Gastroenterol. 2005;11(17):2545–8.CrossRefPubMedPubMedCentral
23.
go back to reference Melle C, Ernst G, Schimmel B, Bleul A, Kaufmann R, Hommann M, Richter KK, Daffner W, Settmacher U, Claussen U, et al. Characterization of pepsinogen C as a potential biomarker for gastric cancer using a histo-proteomic approach. J Proteome Res. 2005;4(5):1799–804.CrossRefPubMed Melle C, Ernst G, Schimmel B, Bleul A, Kaufmann R, Hommann M, Richter KK, Daffner W, Settmacher U, Claussen U, et al. Characterization of pepsinogen C as a potential biomarker for gastric cancer using a histo-proteomic approach. J Proteome Res. 2005;4(5):1799–804.CrossRefPubMed
24.
go back to reference Xu Q, Sun LP, Wang BG, Liu JW, Li P, He CY, Yuan Y. The co-expression of functional gastric proteins in dynamic gastric diseases and its clinical significance. BMC Clin Pathol. 2013;13(1):21.CrossRefPubMedPubMedCentral Xu Q, Sun LP, Wang BG, Liu JW, Li P, He CY, Yuan Y. The co-expression of functional gastric proteins in dynamic gastric diseases and its clinical significance. BMC Clin Pathol. 2013;13(1):21.CrossRefPubMedPubMedCentral
25.
go back to reference Tatematsu M, Ichinose M, Miki K, Hasegawa R, Kato T, Ito N. Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry. Acta Pathologica Japonica. 1990;40(7):494–504.PubMed Tatematsu M, Ichinose M, Miki K, Hasegawa R, Kato T, Ito N. Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry. Acta Pathologica Japonica. 1990;40(7):494–504.PubMed
26.
go back to reference Steele IA, Dimaline R, Pritchard DM, Peek RM Jr, Wang TC, Dockray GJ, Varro A. Helicobacter and gastrin stimulate Reg1 expression in gastric epithelial cells through distinct promoter elements. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G347–54.CrossRefPubMed Steele IA, Dimaline R, Pritchard DM, Peek RM Jr, Wang TC, Dockray GJ, Varro A. Helicobacter and gastrin stimulate Reg1 expression in gastric epithelial cells through distinct promoter elements. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G347–54.CrossRefPubMed
27.
go back to reference Stemmermann GN, Nomura AM. The relation of pepsinogen group II (PGII) expression to intestinal metaplasia and gastric cancer. Histopathology. 2006;49(1):45–51.CrossRefPubMed Stemmermann GN, Nomura AM. The relation of pepsinogen group II (PGII) expression to intestinal metaplasia and gastric cancer. Histopathology. 2006;49(1):45–51.CrossRefPubMed
28.
go back to reference Fernandez R, Vizoso F, Rodriguez JC, Merino AM, Gonzalez LO, Quintela I, Andicoechea A, Truan N, Diez MC. Expression and prognostic significance of pepsinogen C in gastric carcinoma. Ann Surg Oncol. 2000;7(7):508–14.CrossRefPubMed Fernandez R, Vizoso F, Rodriguez JC, Merino AM, Gonzalez LO, Quintela I, Andicoechea A, Truan N, Diez MC. Expression and prognostic significance of pepsinogen C in gastric carcinoma. Ann Surg Oncol. 2000;7(7):508–14.CrossRefPubMed
29.
go back to reference He CY, Sun LP, Gong YH, Xu Q, Dong NN, Yuan Y. Serum pepsinogen II: a neglected but useful biomarker to differentiate between diseased and normal stomachs. J Gastroenterol Hepatol. 2011;26(6):1039–46.CrossRefPubMed He CY, Sun LP, Gong YH, Xu Q, Dong NN, Yuan Y. Serum pepsinogen II: a neglected but useful biomarker to differentiate between diseased and normal stomachs. J Gastroenterol Hepatol. 2011;26(6):1039–46.CrossRefPubMed
31.
go back to reference Massarrat S, Haj-Sheykholeslami A, Mohamadkhani A, Zendehdel N, Aliasgari A, Rakhshani N, Stolte M, Shahidi SM. Pepsinogen II can be a potential surrogate marker of morphological changes in corpus before and after H. pylori Eradication. Biomed Res Int. 2014;2014:1–7.CrossRef Massarrat S, Haj-Sheykholeslami A, Mohamadkhani A, Zendehdel N, Aliasgari A, Rakhshani N, Stolte M, Shahidi SM. Pepsinogen II can be a potential surrogate marker of morphological changes in corpus before and after H. pylori Eradication. Biomed Res Int. 2014;2014:1–7.CrossRef
32.
go back to reference Sun LP, Gong YH, Yuan Y. Serum pepsinogen concentration as an index for Helicobacter pylori eradication. World Chin J Digestol. 2004;12(8):1827–30. Sun LP, Gong YH, Yuan Y. Serum pepsinogen concentration as an index for Helicobacter pylori eradication. World Chin J Digestol. 2004;12(8):1827–30.
33.
go back to reference Kiyohira K, Yoshihara M, Ito M, Haruma K, Tanaka S, Chayama K. Serum pepsinogen concentration as a marker of Helicobacter pylori infection and the histologic grade of gastritis; evaluation of gastric mucosa by serum pepsinogen levels. J Gastroenterol. 2003;38(4):332–8.CrossRefPubMed Kiyohira K, Yoshihara M, Ito M, Haruma K, Tanaka S, Chayama K. Serum pepsinogen concentration as a marker of Helicobacter pylori infection and the histologic grade of gastritis; evaluation of gastric mucosa by serum pepsinogen levels. J Gastroenterol. 2003;38(4):332–8.CrossRefPubMed
34.
go back to reference Samloff IM, Varis K, Ihamaki T, Siurala M, Rotter JI. Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology. 1982;83(1 Pt 2):204–9.PubMed Samloff IM, Varis K, Ihamaki T, Siurala M, Rotter JI. Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology. 1982;83(1 Pt 2):204–9.PubMed
35.
go back to reference Li HM, Ning PF, Yuan Y. The contrastive study between the PGC tissue expression and PGs Serum levels in different gastric mucosa diseases. Chin J Cancer Res. 2006;18(1):8–11.CrossRef Li HM, Ning PF, Yuan Y. The contrastive study between the PGC tissue expression and PGs Serum levels in different gastric mucosa diseases. Chin J Cancer Res. 2006;18(1):8–11.CrossRef
36.
go back to reference Miki K, Ichinose M, Ishikawa KB, Yahagi N, Matsushima M, Kakei N, Tsukada S, Kido M, Ishihama S, Shimizu Y, et al. Clinical application of serum pepsinogen I and II levels for mass screening to detect gastric cancer. Jap J Cancer Res. 1993;84(10):1086–90.CrossRef Miki K, Ichinose M, Ishikawa KB, Yahagi N, Matsushima M, Kakei N, Tsukada S, Kido M, Ishihama S, Shimizu Y, et al. Clinical application of serum pepsinogen I and II levels for mass screening to detect gastric cancer. Jap J Cancer Res. 1993;84(10):1086–90.CrossRef
37.
go back to reference Sun L-P, Gong Y-H, Wang L, Yuan Y. Serum pepsinogen levels and their influencing factors: a population-based study in 6990 Chinese from North China. World J Gastroenterol. 2007;13(48):6562–7.CrossRefPubMedPubMedCentral Sun L-P, Gong Y-H, Wang L, Yuan Y. Serum pepsinogen levels and their influencing factors: a population-based study in 6990 Chinese from North China. World J Gastroenterol. 2007;13(48):6562–7.CrossRefPubMedPubMedCentral
38.
go back to reference Tu H, Sun L, Dong X, Gong Y, Xu Q, Jing J, Long Q, Flanders WD, Bostick RM, Yuan Y. Temporal changes in serum biomarkers and risk for progression of gastric precancerous lesions: a longitudinal study. Int J Cancer. 2015;136(2):425–34.CrossRefPubMed Tu H, Sun L, Dong X, Gong Y, Xu Q, Jing J, Long Q, Flanders WD, Bostick RM, Yuan Y. Temporal changes in serum biomarkers and risk for progression of gastric precancerous lesions: a longitudinal study. Int J Cancer. 2015;136(2):425–34.CrossRefPubMed
39.
go back to reference Xie Y, Zhi X, Su H, Wang K, Yan Z, He N, Zhang J, Chen D, Cui D. A novel electrochemical microfluidic chip combined with multiple biomarkers for early diagnosis of gastric cancer. Nanoscale Res Lett. 2015;10(1):477.CrossRefPubMedPubMedCentral Xie Y, Zhi X, Su H, Wang K, Yan Z, He N, Zhang J, Chen D, Cui D. A novel electrochemical microfluidic chip combined with multiple biomarkers for early diagnosis of gastric cancer. Nanoscale Res Lett. 2015;10(1):477.CrossRefPubMedPubMedCentral
40.
go back to reference Cao XY, Jia ZF, Jin MS, Cao DH, Kong F, Suo J, Jiang J. Serum pepsinogen II is a better diagnostic marker in gastric cancer. World J Gastroenterol. 2012;18(48):7357–61.CrossRefPubMedPubMedCentral Cao XY, Jia ZF, Jin MS, Cao DH, Kong F, Suo J, Jiang J. Serum pepsinogen II is a better diagnostic marker in gastric cancer. World J Gastroenterol. 2012;18(48):7357–61.CrossRefPubMedPubMedCentral
41.
go back to reference Huang YK, Yu JC, Kang WM, Ma ZQ, Ye X, Tian SB, Yan C. Significance of serum pepsinogens as a biomarker for gastric cancer and atrophic gastritis screening: a systematic review and meta-analysis. PLoS ONE. 2015;10(11):e0142080.CrossRefPubMedPubMedCentral Huang YK, Yu JC, Kang WM, Ma ZQ, Ye X, Tian SB, Yan C. Significance of serum pepsinogens as a biomarker for gastric cancer and atrophic gastritis screening: a systematic review and meta-analysis. PLoS ONE. 2015;10(11):e0142080.CrossRefPubMedPubMedCentral
42.
go back to reference Yeh JM, Hur C, Ward Z, Schrag D, Goldie SJ. Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis. Gut. 2016;65(4):563–74.CrossRefPubMed Yeh JM, Hur C, Ward Z, Schrag D, Goldie SJ. Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis. Gut. 2016;65(4):563–74.CrossRefPubMed
43.
go back to reference Ito K, Koizuka H, Suzuki K, Okubo K, Aoki Y, Yada T, Akazawa N, Aoyanagi N, Ishida T, Uemura N. A case of intraductal papillary mucinous neoplasm with high serum pepsinogen II level. Nihon Shokakibyo Gakkai zasshi. Jap J Gastro-enterol. 2016;113(8):1416–24. Ito K, Koizuka H, Suzuki K, Okubo K, Aoki Y, Yada T, Akazawa N, Aoyanagi N, Ishida T, Uemura N. A case of intraductal papillary mucinous neoplasm with high serum pepsinogen II level. Nihon Shokakibyo Gakkai zasshi. Jap J Gastro-enterol. 2016;113(8):1416–24.
44.
go back to reference Yada T, Ito K, Suzuki K, Okubo K, Aoki Y, Akazawa N, Koizuka H, Ishida T, Uemura N. Marked decrease in serum pepsinogen II levels resulting from endoscopic resection of a large duodenal tumor. Clin J Gastroenterol. 2014;7(6):484–9.CrossRefPubMedPubMedCentral Yada T, Ito K, Suzuki K, Okubo K, Aoki Y, Akazawa N, Koizuka H, Ishida T, Uemura N. Marked decrease in serum pepsinogen II levels resulting from endoscopic resection of a large duodenal tumor. Clin J Gastroenterol. 2014;7(6):484–9.CrossRefPubMedPubMedCentral
45.
go back to reference Yu G, Gail MH, Shi J, Klepac-Ceraj V, Paster BJ, Dye BA, Wang GQ, Wei WQ, Fan JH, Qiao YL, et al. Association between upper digestive tract microbiota and cancer-predisposing states in the esophagus and stomach. Cancer Epidemiol Biomark Prev. 2014;23(5):735–41.CrossRef Yu G, Gail MH, Shi J, Klepac-Ceraj V, Paster BJ, Dye BA, Wang GQ, Wei WQ, Fan JH, Qiao YL, et al. Association between upper digestive tract microbiota and cancer-predisposing states in the esophagus and stomach. Cancer Epidemiol Biomark Prev. 2014;23(5):735–41.CrossRef
46.
go back to reference Kamangar F, Diaw L, Wei WQ, Abnet CC, Wang GQ, Roth MJ, Liu B, Lu N, Giffen C, Qiao YL, et al. Serum pepsinogens and risk of esophageal squamous dysplasia. Int J Cancer. 2009;124(2):456–60.CrossRefPubMedPubMedCentral Kamangar F, Diaw L, Wei WQ, Abnet CC, Wang GQ, Roth MJ, Liu B, Lu N, Giffen C, Qiao YL, et al. Serum pepsinogens and risk of esophageal squamous dysplasia. Int J Cancer. 2009;124(2):456–60.CrossRefPubMedPubMedCentral
47.
go back to reference Truan N, Vizoso F, Fresno MF, Fernandez R, Quintela I, Alexandre E, Martinez A. Expression and clinical significance of pepsinogen C in resectable pancreatic cancer. Int J Biol Mark. 2001;16(1):31–6. Truan N, Vizoso F, Fresno MF, Fernandez R, Quintela I, Alexandre E, Martinez A. Expression and clinical significance of pepsinogen C in resectable pancreatic cancer. Int J Biol Mark. 2001;16(1):31–6.
48.
go back to reference Merino AM, Vazquez J, Rodriguez JC, Fernandez R, Quintela I, Gonzalez LO, Sanchez LM, Vizoso F. Pepsinogen C expression in tumors of extragastric origin. Int J Biol Mark. 2000;15(2):165–70. Merino AM, Vazquez J, Rodriguez JC, Fernandez R, Quintela I, Gonzalez LO, Sanchez LM, Vizoso F. Pepsinogen C expression in tumors of extragastric origin. Int J Biol Mark. 2000;15(2):165–70.
49.
go back to reference Alvarez ML, Barbon JJ, Gonzalez LO, Lamelas ML, Vazquez J, Vizoso FJ. Expression of two androgen-induced proteins (pepsinogen C and apolipoprotein d) in epithelial skin cancers of the eyelids. Ophthalmologica. 2004;218(2):115–9.CrossRefPubMed Alvarez ML, Barbon JJ, Gonzalez LO, Lamelas ML, Vazquez J, Vizoso FJ. Expression of two androgen-induced proteins (pepsinogen C and apolipoprotein d) in epithelial skin cancers of the eyelids. Ophthalmologica. 2004;218(2):115–9.CrossRefPubMed
50.
go back to reference Quintela I, Vizoso F, Serra C, Gonzalez LO, Fernandez R, Merino AM, Baltasar A. Immunohistochemical study of pepsinogen C expression in cutaneous malignant melanoma: association with clinicopathological parameters. Int J Biol Mark. 2001;16(4):240–4. Quintela I, Vizoso F, Serra C, Gonzalez LO, Fernandez R, Merino AM, Baltasar A. Immunohistochemical study of pepsinogen C expression in cutaneous malignant melanoma: association with clinicopathological parameters. Int J Biol Mark. 2001;16(4):240–4.
51.
go back to reference Balbin M, Lopez-Otin C. Hormonal regulation of the human pepsinogen C gene in breast cancer cells. Identification of a cis-acting element mediating its induction by androgens, glucocorticoids, and progesterone. J Biol Chem. 1996;271(25):15175–81.CrossRefPubMed Balbin M, Lopez-Otin C. Hormonal regulation of the human pepsinogen C gene in breast cancer cells. Identification of a cis-acting element mediating its induction by androgens, glucocorticoids, and progesterone. J Biol Chem. 1996;271(25):15175–81.CrossRefPubMed
52.
go back to reference Tenti P, Aguzzi A, Riva C, Usellini L, Zappatore R, Bara J, Samloff IM, Solcia E. Ovarian mucinous tumors frequently express markers of gastric, intestinal, and pancreatobiliary epithelial cells. Cancer. 1992;69(8):2131–42.CrossRefPubMed Tenti P, Aguzzi A, Riva C, Usellini L, Zappatore R, Bara J, Samloff IM, Solcia E. Ovarian mucinous tumors frequently express markers of gastric, intestinal, and pancreatobiliary epithelial cells. Cancer. 1992;69(8):2131–42.CrossRefPubMed
53.
go back to reference Rothacker D, Knolle J, Stiller D, Borchard F. Primary retroperitoneal mucinous cystadenomas with gastric epithelial differentiation. Pathol Res Pract. 1993;189(10):1195–204.CrossRefPubMed Rothacker D, Knolle J, Stiller D, Borchard F. Primary retroperitoneal mucinous cystadenomas with gastric epithelial differentiation. Pathol Res Pract. 1993;189(10):1195–204.CrossRefPubMed
54.
go back to reference Fukushima N, Sato N, Prasad N, Leach SD, Hruban RH, Goggins M. Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays. Oncogene. 2004;23(56):9042–51.CrossRefPubMed Fukushima N, Sato N, Prasad N, Leach SD, Hruban RH, Goggins M. Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays. Oncogene. 2004;23(56):9042–51.CrossRefPubMed
55.
go back to reference Miyasaka Y, Enomoto N, Nagayama K, Izumi N, Marumo F, Watanabe M, Sato C. Analysis of differentially expressed genes in human hepatocellular carcinoma using suppression subtractive hybridization. Br J Cancer. 2001;85(2):228–34.CrossRefPubMedPubMedCentral Miyasaka Y, Enomoto N, Nagayama K, Izumi N, Marumo F, Watanabe M, Sato C. Analysis of differentially expressed genes in human hepatocellular carcinoma using suppression subtractive hybridization. Br J Cancer. 2001;85(2):228–34.CrossRefPubMedPubMedCentral
56.
go back to reference Nakamura T, Suzuki T, Kobayashi S, Matsuura A, Shirai M, Tatematsu K, Yamachika T, Tatematsu M. Histochemical and immunohistochemical study of human gastric carcinoma differentiation with special reference to supplementary role for endosonography in evaluating depth of invasion. J Gastroenterol. 1997;32(2):176–83.CrossRefPubMed Nakamura T, Suzuki T, Kobayashi S, Matsuura A, Shirai M, Tatematsu K, Yamachika T, Tatematsu M. Histochemical and immunohistochemical study of human gastric carcinoma differentiation with special reference to supplementary role for endosonography in evaluating depth of invasion. J Gastroenterol. 1997;32(2):176–83.CrossRefPubMed
58.
go back to reference Liu HJ, Guo XL, Dong M, Wang L, Yuan Y. Association between pepsinogen C gene polymorphism and genetic predisposition to gastric cancer. World J Gastroenterol. 2003;9(1):50–3.CrossRefPubMedPubMedCentral Liu HJ, Guo XL, Dong M, Wang L, Yuan Y. Association between pepsinogen C gene polymorphism and genetic predisposition to gastric cancer. World J Gastroenterol. 2003;9(1):50–3.CrossRefPubMedPubMedCentral
59.
go back to reference Sun LP, Gong YH, Dong NN, Wang L, Yuan Y. Correlation of pepsinogen C (PGC) gene insertion/deletion polymorphism to PGC protein expression in gastric mucosa and serum. Ai zheng Aizheng Chin J Cancer. 2009;28(5):487–92. Sun LP, Gong YH, Dong NN, Wang L, Yuan Y. Correlation of pepsinogen C (PGC) gene insertion/deletion polymorphism to PGC protein expression in gastric mucosa and serum. Ai zheng Aizheng Chin J Cancer. 2009;28(5):487–92.
60.
go back to reference Kumar S, Kumari N, Mittal RD, Ghoshal UC. Pepsinogen-II 100 bp ins/del gene polymorphism and its elevated circulating levels are associated with gastric cancer, particularly with Helicobacter pylori infection and intestinal metaplasia. Gastric Cancer. 2016;19(3):808–16.CrossRefPubMed Kumar S, Kumari N, Mittal RD, Ghoshal UC. Pepsinogen-II 100 bp ins/del gene polymorphism and its elevated circulating levels are associated with gastric cancer, particularly with Helicobacter pylori infection and intestinal metaplasia. Gastric Cancer. 2016;19(3):808–16.CrossRefPubMed
61.
go back to reference Pinto-Correia AL, Sousa H, Fragoso M, Moreira-Dias L, Lopes C, Medeiros R, Dinis-Ribeiro M. Gastric cancer in a Caucasian population: role of pepsinogen C genetic variants. World J Gastroenterol. 2006;12(31):5033–6.CrossRefPubMedPubMedCentral Pinto-Correia AL, Sousa H, Fragoso M, Moreira-Dias L, Lopes C, Medeiros R, Dinis-Ribeiro M. Gastric cancer in a Caucasian population: role of pepsinogen C genetic variants. World J Gastroenterol. 2006;12(31):5033–6.CrossRefPubMedPubMedCentral
62.
go back to reference He C, Tu H, Sun L, Xu Q, Li P, Gong Y, Dong N, Yuan Y. Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case–control study in Chinese. Carcinogenesis. 2013;34(7):1450–7.CrossRefPubMed He C, Tu H, Sun L, Xu Q, Li P, Gong Y, Dong N, Yuan Y. Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case–control study in Chinese. Carcinogenesis. 2013;34(7):1450–7.CrossRefPubMed
63.
go back to reference He CY, Sun LP, Xu Q, Liu JW, Jiang JY, Dong NN, Yuan Y. PGC TagSNP and its interaction with H. pylori and relation with gene expression in susceptibility to gastric carcinogenesis. PLoS ONE. 2014;9(12):e115955.CrossRefPubMedPubMedCentral He CY, Sun LP, Xu Q, Liu JW, Jiang JY, Dong NN, Yuan Y. PGC TagSNP and its interaction with H. pylori and relation with gene expression in susceptibility to gastric carcinogenesis. PLoS ONE. 2014;9(12):e115955.CrossRefPubMedPubMedCentral
64.
go back to reference He C, Xu Q, Tu H, Sun L, Gong Y, Liu J, Yuan Y. Polymorphic rs9471643 and rs6458238 upregulate PGC transcription and protein expression in overdominant or dominant models. Mol Carcinog. 2016;55(5):586–99.CrossRefPubMed He C, Xu Q, Tu H, Sun L, Gong Y, Liu J, Yuan Y. Polymorphic rs9471643 and rs6458238 upregulate PGC transcription and protein expression in overdominant or dominant models. Mol Carcinog. 2016;55(5):586–99.CrossRefPubMed
65.
go back to reference Niwa T, Yamashita S, Tsukamoto T, Kuramoto T, Nomoto T, Wakazono K, Fujita H, Matsushima T, Tatematsu M, Sugimura T, et al. Whole-genome analyses of loss of heterozygosity and methylation analysis of four tumor-suppressor genes in N-methyl-N’-nitro-N-nitrosoguanidine-induced rat stomach carcinomas. Cancer Sci. 2005;96(7):409–13.CrossRefPubMed Niwa T, Yamashita S, Tsukamoto T, Kuramoto T, Nomoto T, Wakazono K, Fujita H, Matsushima T, Tatematsu M, Sugimura T, et al. Whole-genome analyses of loss of heterozygosity and methylation analysis of four tumor-suppressor genes in N-methyl-N’-nitro-N-nitrosoguanidine-induced rat stomach carcinomas. Cancer Sci. 2005;96(7):409–13.CrossRefPubMed
66.
go back to reference Perlmann GE. Acetylation of pepsin and pepsinogen. J Biol Chem. 1966;241(1):153–7.PubMed Perlmann GE. Acetylation of pepsin and pepsinogen. J Biol Chem. 1966;241(1):153–7.PubMed
67.
go back to reference Liu WJ, Xu Q, Sun LP, Dong QG, He CY, Yuan Y. Expression of serum let-7c, let-7i, and let-7f microRNA with its target gene, pepsinogen C, in gastric cancer and precancerous disease. Tumour Biol. 2015;36(5):3337–43.CrossRefPubMed Liu WJ, Xu Q, Sun LP, Dong QG, He CY, Yuan Y. Expression of serum let-7c, let-7i, and let-7f microRNA with its target gene, pepsinogen C, in gastric cancer and precancerous disease. Tumour Biol. 2015;36(5):3337–43.CrossRefPubMed
68.
go back to reference Fassan M, Saraggi D, Balsamo L, Cascione L, Castoro C, Coati I, De Bernard M, Farinati F, Guzzardo V, Valeri N, et al. Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis. Oncotarget. 2016;7(4):4915–24.PubMed Fassan M, Saraggi D, Balsamo L, Cascione L, Castoro C, Coati I, De Bernard M, Farinati F, Guzzardo V, Valeri N, et al. Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis. Oncotarget. 2016;7(4):4915–24.PubMed
69.
go back to reference Xu Q, Dong QG, Sun LP, He CY, Yuan Y. Expression of serum miR-20a-5p, let-7a, and miR-320a and their correlations with pepsinogen in atrophic gastritis and gastric cancer: a case–control study. BMC Clin Pathol. 2013;13:11.CrossRefPubMedPubMedCentral Xu Q, Dong QG, Sun LP, He CY, Yuan Y. Expression of serum miR-20a-5p, let-7a, and miR-320a and their correlations with pepsinogen in atrophic gastritis and gastric cancer: a case–control study. BMC Clin Pathol. 2013;13:11.CrossRefPubMedPubMedCentral
70.
go back to reference Diez-Itza I, Merino AM, Tolivia J, Vizoso F, Sanchez LM, Lopez-Otin C. Expression of pepsinogen C in human breast tumours and correlation with clinicopathologic parameters. Br J Cancer. 1993;68(3):637–40.CrossRefPubMedPubMedCentral Diez-Itza I, Merino AM, Tolivia J, Vizoso F, Sanchez LM, Lopez-Otin C. Expression of pepsinogen C in human breast tumours and correlation with clinicopathologic parameters. Br J Cancer. 1993;68(3):637–40.CrossRefPubMedPubMedCentral
71.
go back to reference Konishi N, Nakaoka S, Matsumoto K, Nakamura M, Kuwashima S, Hiasa Y, Cho M, Uemura H, Hirao Y. Expression of pepsinogen II with androgen and estrogen receptors in human prostate carcinoma. Pathol Int. 1999;49(3):203–7.CrossRefPubMed Konishi N, Nakaoka S, Matsumoto K, Nakamura M, Kuwashima S, Hiasa Y, Cho M, Uemura H, Hirao Y. Expression of pepsinogen II with androgen and estrogen receptors in human prostate carcinoma. Pathol Int. 1999;49(3):203–7.CrossRefPubMed
72.
go back to reference Wells M, Brown B, Hall J. Pepsinogen C expression in intestinal IEC-6 cells. Cell Physiol Biochem. 2003;13(5):301–8.CrossRefPubMed Wells M, Brown B, Hall J. Pepsinogen C expression in intestinal IEC-6 cells. Cell Physiol Biochem. 2003;13(5):301–8.CrossRefPubMed
73.
go back to reference Ishihara T, Ichihara Y, Hayano T, Katsura I, Sogawa K, Fujii-Kuriyama Y, Takahashi K. Primary structure and transcriptional regulation of rat pepsinogen C gene. J Biol Chem. 1989;264(17):10193–9.PubMed Ishihara T, Ichihara Y, Hayano T, Katsura I, Sogawa K, Fujii-Kuriyama Y, Takahashi K. Primary structure and transcriptional regulation of rat pepsinogen C gene. J Biol Chem. 1989;264(17):10193–9.PubMed
74.
go back to reference Fehrholz M, Hutten M, Kramer BW, Speer CP, Kunzmann S. Amplification of steroid-mediated SP-B expression by physiological levels of caffeine. Am J Physiol Lung Cell Mol Physiol. 2014;306(1):L101–9.CrossRefPubMed Fehrholz M, Hutten M, Kramer BW, Speer CP, Kunzmann S. Amplification of steroid-mediated SP-B expression by physiological levels of caffeine. Am J Physiol Lung Cell Mol Physiol. 2014;306(1):L101–9.CrossRefPubMed
75.
go back to reference Tsukada S, Ichinose M, Yahagi N, Matsubara Y, Yonezawa S, Shiokawa K, Furihata C, Miki K, Fukamachi H. Induction of precocious pepsinogen synthesis by glucocorticoids in fetal rat gastric epithelium in organ culture: importance of mesenchyme for epithelial differentiation. Differentiation. 1998;62(5):239–47.CrossRefPubMed Tsukada S, Ichinose M, Yahagi N, Matsubara Y, Yonezawa S, Shiokawa K, Furihata C, Miki K, Fukamachi H. Induction of precocious pepsinogen synthesis by glucocorticoids in fetal rat gastric epithelium in organ culture: importance of mesenchyme for epithelial differentiation. Differentiation. 1998;62(5):239–47.CrossRefPubMed
76.
go back to reference Sakamoto N, Fukuda K, Watanuki K, Sakai D, Komano T, Scotting PJ, Yasugi S. Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial-mesenchymal interactions in the developing chicken stomach. Dev Biol. 2000;223(1):103–13.CrossRefPubMed Sakamoto N, Fukuda K, Watanuki K, Sakai D, Komano T, Scotting PJ, Yasugi S. Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial-mesenchymal interactions in the developing chicken stomach. Dev Biol. 2000;223(1):103–13.CrossRefPubMed
77.
go back to reference Sakamoto N, Saiga H, Yasugi S. Analysis of temporal expression pattern and cis-regulatory sequences of chicken pepsinogen A and C. Biochem Biophys Res Commun. 1998;250(2):420–4.CrossRefPubMed Sakamoto N, Saiga H, Yasugi S. Analysis of temporal expression pattern and cis-regulatory sequences of chicken pepsinogen A and C. Biochem Biophys Res Commun. 1998;250(2):420–4.CrossRefPubMed
78.
go back to reference Huh WJ, Esen E, Geahlen JH, Bredemeyer AJ, Lee AH, Shi G, Konieczny SF, Glimcher LH, Mills JC. XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum. Gastroenterology. 2010;139(6):2038–49.CrossRefPubMedPubMedCentral Huh WJ, Esen E, Geahlen JH, Bredemeyer AJ, Lee AH, Shi G, Konieczny SF, Glimcher LH, Mills JC. XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum. Gastroenterology. 2010;139(6):2038–49.CrossRefPubMedPubMedCentral
79.
go back to reference Blandizzi C, Colucci R, Carignani D, Natale G, Lazzeri G, Crema F, Del Tacca M. Role of peripheral GABAB receptors in the regulation of pepsinogen secretion in anaesthetized rats. Eur J Pharmacol. 1995;294(1):191–200.CrossRefPubMed Blandizzi C, Colucci R, Carignani D, Natale G, Lazzeri G, Crema F, Del Tacca M. Role of peripheral GABAB receptors in the regulation of pepsinogen secretion in anaesthetized rats. Eur J Pharmacol. 1995;294(1):191–200.CrossRefPubMed
80.
go back to reference Sharp R, Babyatsky MW, Takagi H, Tagerud S, Wang TC, Bockman DE, Brand SJ, Merlino G. Transforming growth factor alpha disrupts the normal program of cellular differentiation in the gastric mucosa of transgenic mice. Development. 1995;121(1):149–61.PubMed Sharp R, Babyatsky MW, Takagi H, Tagerud S, Wang TC, Bockman DE, Brand SJ, Merlino G. Transforming growth factor alpha disrupts the normal program of cellular differentiation in the gastric mucosa of transgenic mice. Development. 1995;121(1):149–61.PubMed
81.
go back to reference Wang TC, Bonner-Weir S, Oates PS, Chulak M, Simon B, Merlino GT, Schmidt EV, Brand SJ. Pancreatic gastrin stimulates islet differentiation of transforming growth factor alpha-induced ductular precursor cells. J Clin Invest. 1993;92(3):1349–56.CrossRefPubMedPubMedCentral Wang TC, Bonner-Weir S, Oates PS, Chulak M, Simon B, Merlino GT, Schmidt EV, Brand SJ. Pancreatic gastrin stimulates islet differentiation of transforming growth factor alpha-induced ductular precursor cells. J Clin Invest. 1993;92(3):1349–56.CrossRefPubMedPubMedCentral
82.
go back to reference Li D, Zhang J, Xi Y, Zhang L, Li W, Cui J, Xing R, Pan Y, Pan Z, Li F, et al. Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein induce cell differentiation in gastric cancer. BMC Cancer. 2015;15:637.CrossRefPubMedPubMedCentral Li D, Zhang J, Xi Y, Zhang L, Li W, Cui J, Xing R, Pan Y, Pan Z, Li F, et al. Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein induce cell differentiation in gastric cancer. BMC Cancer. 2015;15:637.CrossRefPubMedPubMedCentral
83.
go back to reference Wen XZ, Miyake S, Akiyama Y, Yuasa Y. BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells. Biochem Biophys Res Commun. 2004;316(1):100–6.CrossRefPubMed Wen XZ, Miyake S, Akiyama Y, Yuasa Y. BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells. Biochem Biophys Res Commun. 2004;316(1):100–6.CrossRefPubMed
Metadata
Title
Pepsinogen C expression, regulation and its relationship with cancer
Authors
Shixuan Shen
Jingyi Jiang
Yuan Yuan
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0426-6

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