Expression of ribophorine II is a promising prognostic factor in human gastric adenocarcinoma

Fujimoto,Daisuke; Goi,Takanori; Hirono,Yasuo

doi:10.3892/ijo.2016.3822

Expression of ribophorine II is a promising prognostic factor in human gastric adenocarcinoma

Authors:
- Daisuke Fujimoto
- Takanori Goi
- Yasuo Hirono
View Affiliations

Affiliations: Department of Surgery 1, Faculty of Medicine, University of Fukui, Fukui 910-1193, Japan
Published online on: December 28, 2016 https://doi.org/10.3892/ijo.2016.3822
Pages: 448-456

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The increased invasiveness of gastric adenocarcinoma is important for progression and metastasis. In recent molecular biological studies, ribophorine II (RPN2) induced epithelial-mesenchymal transition and metastatic activity. However, no studies have evaluated the relationship between RPN2 expression, ability of cancer to invade/metastasis, and patient prognosis in gastric adenocarcinoma. Therefore, we have examined these factors. Immunohistochemical staining was performed to detect RPN2 and p53 in the primary lesion and adjacent normal gastric mucosa of 242 gastric adenocarcinoma patients who underwent resection surgery. We conducted clinicopathologic examinations and analyzed patient prognoses with the Kaplan-Meier method. Further, multivariate analysis was conducted using a Cox hazard model. Also, we analyzed the ability of invasion under inhibited RPN2 expression in vitro. RPN2 expression was observed in 119 of 242 cases of gastric adenocarcinoma patients. RPN2 expression was associated with a higher incidence of depth of wall invasion, lymph node metastasis, lymphatic invasion, venous invasion, peritoneal dissemination, histopathological stage, and p53 expression. In stage II and III curative resection cases, where recurrence is the most serious problem, cases that expressed RPN2 had a significantly lower 5-year survival rate and higher recurrence rate compared to the cases with no RPN2 expression. In the multivariate analysis for prognosis, RPN2 expression was found to be an independent factor. Also, gastric adenocarcinoma cell, had mutant-type p53, reduced the ability of invasion by knockout of RPN2 expression in vitro. RPN2 expression correlates with gastric adenocarcinoma cell invasion and shows promise as a new prognostic factor in human gastric adenocarcinoma.

View Figures

View References

1	Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA and Hamilton SM: Gastric adenocarcinoma: Review and considerations for future directions. Ann Surg. 241:27–39. 2005.
2	Nissan A, Garofalo A and Esquivel J: Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (HIPEC) for gastric adenocarcinoma: Why haven't we reached the promised land? J Surg Oncol. 102:359–360. 2010. View Article : Google Scholar : PubMed/NCBI
3	Glehen O, Mohamed F and Gilly FN: Peritoneal carcinomatosis from digestive tract cancer: New management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol. 5:219–228. 2004. View Article : Google Scholar : PubMed/NCBI
4	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
7	Takei Y, Takigahira M, Mihara K, Tarumi Y and Yanagihara K: The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer. Cancer Res. 71:1442–1453. 2011. View Article : Google Scholar
8	Motoyama K, Inoue H, Mimori K, Tanaka F, Kojima K, Uetake H, Sugihara K and Mori M: Clinicopathological and prognostic significance of PDCD4 and microRNA-21 in human gastric cancer. Int J Oncol. 36:1089–1095. 2010.PubMed/NCBI
9	Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, et al: Relation between microRNA expression and progression and prognosis of gastric cancer: A microRNA expression analysis. Lancet Oncol. 11:136–146. 2010. View Article : Google Scholar
10	Zhang Z, Liu S, Shi R and Zhao G: miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition. Cancer Genet. 204:486–491. 2011. View Article : Google Scholar : PubMed/NCBI
11	Okugawa Y, Inoue Y, Tanaka K, Kawamura M, Saigusa S, Toiyama Y, Ohi M, Uchida K, Mohri Y and Kusunoki M: Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer. Clin Exp Metastasis. 30:417–429. 2013. View Article : Google Scholar
12	Takahashi RU, Takeshita F, Honma K, Ono M, Kato K and Ochiya T: Ribophorin II regulates breast tumor initiation and metastasis through the functional suppression of GSK3β. Sci Rep. 3:24742013. View Article : Google Scholar
13	Japanese Gastric Cancer Association: Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 14:113–123. 2011. View Article : Google Scholar : PubMed/NCBI
14	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
15	Nguyen DX, Bos PD and Massagué J: Metastasis: From dissemination to organ-specific colonization. Nat Rev Cancer. 9:274–284. 2009. View Article : Google Scholar : PubMed/NCBI
16	Löffler C, Rao VV and Hansmann I: Mapping of the ribophorin II (RPN II) gene to human chromosome 20q12–q13.1 by in-situ hybridization. Hum Genet. 87:221–222. 1991. View Article : Google Scholar
17	Testa JR, Kinnealey A, Rowley JD, Golde DW and Potter D: Deletion of the long arm of chromosome 20 [del(20)(q11)] in myeloid disorders. Blood. 52:868–877. 1978.PubMed/NCBI
18	Kelleher DJ, Kreibich G and Gilmore R: Oligosaccharyltransferase activity is associated with a protein complex composed of ribophorins I and II and a 48 kd protein. Cell. 69:55–65. 1992. View Article : Google Scholar : PubMed/NCBI
19	Kelleher DJ and Gilmore R: An evolving view of the eukaryotic oligosaccharyltransferase. Glycobiology. 16:47R–62R. 2006. View Article : Google Scholar
20	Honma K, Iwao-Koizumi K, Takeshita F, Yamamoto Y, Yoshida T, Nishio K, Nagahara S, Kato K and Ochiya T: RPN2 gene confers docetaxel resistance in breast cancer. Nat Med. 14:939–948. 2008. View Article : Google Scholar : PubMed/NCBI
21	Chen QY, Jiao DM, Wang J, Hu H, Tang X, Chen J, Mou H and Lu W: miR-206 regulates cisplatin resistance and EMT in human lung adenocarcinoma cells partly by targeting MET. Oncotarget. 7:24510–24526. 2016.PubMed/NCBI
22	Zhao JJ, Chu ZB, Hu Y, Lin J, Wang Z, Jiang M, Chen M, Wang X, Kang Y, Zhou Y, et al: Targeting the miR-221-222/PUMA/BAK/BAX pathway abrogates dexamethasone resistance in multiple myeloma. Cancer Res. 75:4384–4397. 2015. View Article : Google Scholar : PubMed/NCBI
23	Ma J, Fang B, Zeng F, Ma C, Pang H, Cheng L, Shi Y, Wang H, Yin B, Xia J, et al: Down-regulation of miR-223 reverses epithelial-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Oncotarget. 6:1740–1749. 2015. View Article : Google Scholar : PubMed/NCBI
24	Yukimoto K, Nakata B, Muguruma K, Yashiro M, Ohira M, Ishikawa T, Hino M and Hirakawa K: Apoptosis and thymidylate synthase inductions by 5-fluorouracil in gastric cancer cells with or without p53 mutation. Int J Oncol. 19:373–378. 2001.PubMed/NCBI
25	Endo F, Nishizuka SS, Kume K, Ishida K, Katagiri H, Ishida K, Sato K, Iwaya T, Koeda K and Wakabayashi G: A compensatory role of NF-κB to p53 in response to 5-FU-based chemotherapy for gastric cancer cell lines. PLoS One. 9:e901552014. View Article : Google Scholar
26	Fujita Y, Yagishita S, Takeshita F, Yamamoto Y, Kuwano K and Ochiya T: Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer. Oncotarget. 6:3335–3345. 2015. View Article : Google Scholar : PubMed/NCBI
27	Boyer B, Vallés AM and Edme N: Induction and regulation of epithelial-mesenchymal transitions. Biochem Pharmacol. 60:1091–1099. 2000. View Article : Google Scholar : PubMed/NCBI
28	Kim T, Veronese A, Pichiorri F, Lee TJ, Jeon YJ, Volinia S, Pineau P, Marchio A, Palatini J, Suh SS, et al: p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 208:875–883. 2011. View Article : Google Scholar : PubMed/NCBI