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Open Access 01-12-2017 | Research article

Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes disease progression in human gastric cancer

Authors: Xiangbin Xing, Weibin Cai, Sanmei Ma, Yongfei Wang, Huijuan Shi, Ming Li, Jinxia Jiao, Yang Yang, Longshan Liu, Xiangliang Zhang, Minhu Chen

Published in: BMC Cancer | Issue 1/2017

Abstract

Background

OPCML belongs to the IgLON family of Ig domain–containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear.

Methods

We assessed expression and biological behavior of OPCML in gastric cancer.

Results

OPCML expression was markedly reduced in tumor tissues and cancer cell lines. Decreased OPCML expression had a significant association with unfavorable tumor stage (p = 0.007) and grading (p < 0.001). Furthermore, the results revealed that OPCML was an independent prognostic factor for overall survival in gastric cancer (p = 0.002). In addition, ectopic expression of OPCML in cancer cells significantly inhibited cell viability (p < 0.01) and colony formation (p < 0.001), arrest cell cycle in G0/G1 phase and induced apoptosis, and suppressed tumor formation in nude mice. The alterations of phosphorylation status of AKT and its substrate GSK3β, up-regulation of pro-apoptotic regulators including caspase-3, caspase-9 and PARP, and up-regulation of cell cycle regulator p27, were implicated in the biological activity of OPCML in cancer cells.

Conclusion

Down-regulated OPCML expression might serve as an independent predictor for unfavorable prognosis of patients, and the biological behavior supports its role as a tumor suppressor in gastric cancer.

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Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed

Ebert M, Xing X, Burgermeister E, Schmid R, Röcken C. Perspectives of clinical proteomics in gastrointestinal cancer. Expert Rev Anticancer Ther. 2007;7:465–9.CrossRefPubMed

Chiba T, Marusawa H, Ushijima T. Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation. Gastroenterology. 2012;143:550–63.CrossRefPubMed

Luo D, Zhang B, Lv L, Xiang S, Liu Y, Ji J, Deng D. Methylation of CpG islands of p16 associated with progression of primary gastric carcinomas. Lab Investig. 2006;86:591–8.PubMed

Tsuchiya T, Tamura G, Sato K, Endoh Y, Sakata K, Jin Z, et al. Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia. Oncogene. 2000;19:3642–6.CrossRefPubMed

Xing X, Tang YB, Yuan G, Wang Y, Wang J, Yang Y, Chen M. The prognostic value of E-cadherin in gastric cancer: a meta-analysis. Int J Cancer. 2013;132:2589–96.CrossRefPubMed

Cho TM, Hasegawa J, Ge BL, Loh HH. Purification to apparent homogeneity of a mu-type opioid receptor from rat brain. Proc Natl Acad Sci U S A. 1986;83:4138–42.CrossRefPubMedPubMedCentral

Shark KB, Lee NM. Cloning, sequencing and localization to chromosome 11 of a cDNA encoding a human opioid-binding cell adhesion molecule (OBCAM). Gene. 1995;155:213–7.CrossRefPubMed

Sellar GC, Watt KP, Rabiasz GJ, Stronach EA, Li L, Miller EP, et al. OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer. Nat Genet. 2003;34:337–43.CrossRefPubMed

10.

Wang L, Zhu JS, Song MQ, Chen GQ, Chen JL. Comparison of gene expression profiles between primary tumor and metastatic lesions in gastric cancer patients using laser microdissection and cDNA microarray. World J Gastroenterol. 2006;12:6949–54.CrossRefPubMedPubMedCentral

11.

Cui Y, Ying Y, van Hasselt A, Ng KM, Yu J, Zhang Q, et al. OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PLoS One. 2008;3(8):e2990.CrossRefPubMedPubMedCentral

12.

Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumors. 7th ed. Oxford: Wiley-Blackwell; 2009.

13.

Meng F, Li H, Shi H, Yang Q, Zhang F, Yang Y, et al. MACC1 down-regulation inhibits proliferation and tumourigenicity of nasopharyngeal carcinoma cells through Akt/β-catenin signaling pathway. PLoS One. 2013;8:e60821.CrossRefPubMedPubMedCentral

14.

Xing X, Burgermeister E, Geisler F, Einwächter H, Fan L, Hiber M, et al. Hematopoietically expressed homeobox is a target gene of farnesoid X receptor in chenodeoxycholic acid-induced liver hypertrophy. Hepatology. 2009;49:979–88.CrossRefPubMed

15.

Gu P, Xing X, Tänzer M, Röcken C, Weichert W, Ivanauskas A, et al. Frequent loss of TIMP-3 expression in progression of esophageal and gastric adenocarcinomas. Neoplasia. 2008;10:563–72.CrossRefPubMedPubMedCentral

16.

Burgermeister E, Xing X, Röcken C, Juhasz M, Chen J, Hiber M, et al. Differential expression and function of caveolin-1 in human gastric cancer progression. Cancer Res. 2007;67:8519–26.CrossRefPubMed

17.

Xu L, Li X, Chu ES, Zhao G, Go MY, Tao Q, et al. Epigenetic inactivation of BCL6B, a novel functional tumour suppressor for gastric cancer, is associated with poor survival. Gut. 2012;61:977–85.CrossRefPubMed

18.

Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, Shishido N, et al. Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell. 1996;85:707–20.CrossRefPubMed

19.

Sherr CJ. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 2000;60:3689–95.PubMed

20.

Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A. 2001;98:10983–5.CrossRefPubMedPubMedCentral

21.

Dillon RL, Muller WJ. Distinct biological roles for the akt family in mammary tumor progression. Cancer Res. 2010;70:4260–4.CrossRefPubMedPubMedCentral

22.

Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129:1261–74.CrossRefPubMedPubMedCentral

23.

Xing XB, Chen MH, Li M, Jiao JX. Low expression of OPCML predicts an unfavorable prognosis and promotes disease progression in gastric cancer. J Dig Dis. 2015; http://onlinelibrary.wiley.com/doi/10.1111/1751-2980.12277/full Accessed 31 Aug 2015.

Title: Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes disease progression in human gastric cancer
Authors: Xiangbin Xing
Weibin Cai
Sanmei Ma
Yongfei Wang
Huijuan Shi
Ming Li
Jinxia Jiao
Yang Yang
Longshan Liu
Xiangliang Zhang
Minhu Chen
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-017-3203-y

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