High ADAMTS18 expression is associated with poor prognosis in stomach adenocarcinoma

Jiang,Kaiyuan; Li,Lei; Xie,Yubo; Xie,Dongyi; Xiao,Qiang

doi:10.3892/ol.2020.12074

High ADAMTS18 expression is associated with poor prognosis in stomach adenocarcinoma

Authors:
- Kaiyuan Jiang
- Lei Li
- Yubo Xie
- Dongyi Xie
- Qiang Xiao
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Affiliations: Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Gastrointestinal Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: September 8, 2020 https://doi.org/10.3892/ol.2020.12074
Article Number: 211
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Stomach adenocarcinoma (STAD) is the most pathological type of gastric cancer. ADAM metallopeptidase with thrombospondin type 1 motif 18 (ADAMTS18) plays an essential role in organ development and tumorigenesis; however, its function in STAD, and its impact on clinical outcome remain unclear. Thus, the present study aimed to investigate the association between ADAMTS18 expression and the prognosis of patients with STAD. Data from 300 patients with STAD in The Cancer Genome Atlas (TCGA) database were analyzed, and the median survival time and overall survival (OS) rate of these patients were assessed. Subsequently, 40 paired tumor and non‑tumor tissue samples from patients with STAD were collected, and the relative ADAMTS18 mRNA expression levels were determined. Results from TCGA database demonstrated that high tumor ADAMTS18 expression was associated with a poorer prognosis in patients with STAD. Similarly, results from the assessed patient cohort indicated that ADAMTS18 expression was significantly higher in STAD tissues compared with non‑tumor tissues. Furthermore, ADAMTS18 expression was significantly associated with tumor differentiation, lymph node metastasis and tumor node metastasis stage. Taken together, these results suggest that ADAMTS18 is highly expressed in STAD tissues, and thus may act as a potential indicator of poor prognosis in patients with STAD.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Okines A, Verheij M, Allum W, Cunningham D and Cervantes A; ESMO Guidelines Working Group, : Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21 (Suppl 5):v50–v54. 2010. View Article : Google Scholar : PubMed/NCBI
4	Wei J, Liu CJ and Li Z: ADAMTS-18: A metalloproteinase with multiple functions. Front Biosci (Landmark Ed). 19:1456–1467. 2014. View Article : Google Scholar : PubMed/NCBI
5	Ataca D, Caikovski M, Piersigilli A, Moulin A, Benarafa C, Earp SE, Guri Y, Kostic C, Arsenijevic Y, Soininen R, et al: Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development. Biol Open. 5:1585–1594. 2016. View Article : Google Scholar : PubMed/NCBI
6	Kelwick R, Desanlis I, Wheeler GN and Edwards DR: The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome Biol. 16:1132015. View Article : Google Scholar : PubMed/NCBI
7	Xu H, Xiao Q, Fan Y, Xiang T, Li C, Li C, Li S, Hui T, Zhang L, Li H, et al: Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-κB signaling. Cancer Med. 6:1399–1408. 2017. View Article : Google Scholar : PubMed/NCBI
8	Zhang L, Liu Y and Zheng P: Downregulation of ADAMTS18 May serve as a poor prognostic biomarker for cervical cancer patients. Appl Immunohistochem Mol Morphol. 26:670–675. 2018.PubMed/NCBI
9	Jin H, Wang X, Ying J, Wong AH, Li H, Lee KY, Srivastava G, Chan AT, Yeo W, Ma BB, et al: Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas. Oncogene. 26:7490–7498. 2007. View Article : Google Scholar : PubMed/NCBI
10	Tomczak K, Czerwińska P and Wiznerowicz M: The cancer genome atlas (TCGA): An immeasurable source of knowledge. Contemp Oncol (Pozn). 19:A68–A77. 2015.PubMed/NCBI
11	Cancer Genome Atlas Research Network, . Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513:202–209. 2014. View Article : Google Scholar : PubMed/NCBI
12	Brierley JD, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumours. 8th. John Wiley & Sons; Hoboken, NJ, USA: 2017
13	Batey L, Moon JE, Yu Y, Wu B, Hirschhorn JN, Shen Y and Dauber A: A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency. J Clin Endocrinol Metab. 99:E153–E159. 2014. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI
16	Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, et al: STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47(D1): D607–D613. 2019. View Article : Google Scholar : PubMed/NCBI
17	López-Otín C and Matrisian LM: Emerging roles of proteases in tumour suppression. Nat Rev Cancer. 7:800–808. 2007. View Article : Google Scholar : PubMed/NCBI
18	Kumar S, Rao N and Ge R: Emerging roles of ADAMTSs in angiogenesis and cancer. Cancers (Basel). 4:1252–1299. 2012. View Article : Google Scholar : PubMed/NCBI
19	Wagstaff L, Kelwick R, Decock J and Edwards DR: The roles of ADAMTS metalloproteinases in tumorigenesis and metastasis. Front Biosci (Landmark Ed). 16:1861–1872. 2011. View Article : Google Scholar : PubMed/NCBI
20	Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA and Flannery CR: Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: Comparative analyses with ADAMTS-5, −9, −16 and −18. Biochim Biophys Acta. 1760:517–524. 2006. View Article : Google Scholar : PubMed/NCBI
21	Li Z, Nardi MA, Li YS, Zhang W, Pan R, Dang S, Yee H, Quartermain D, Jonas S and Karpatkin S: C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke. Blood. 113:6051–6060. 2009. View Article : Google Scholar : PubMed/NCBI
22	Li Z, Zhang W, Shao Y, Zhang C, Wu Q, Yang H, Wan X, Zhang J, Guan M, Wan J and Yu B: High-resolution melting analysis of ADAMTS18 methylation levels in gastric, colorectal and pancreatic cancers. Med Oncol. 27:998–1004. 2010. View Article : Google Scholar : PubMed/NCBI
23	Esteller M: Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 8:286–298. 2007. View Article : Google Scholar : PubMed/NCBI
24	Wei X, Prickett TD, Viloria CG, Molinolo A, Lin JC, Cardenas-Navia I, Cruz P; NISC Comparative Sequencing Program, ; Rosenberg SA, Davies MA, et al: Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma. Mol Cancer Res. 8:1513–1525. 2010. View Article : Google Scholar : PubMed/NCBI
25	Malik R, Lelkes PI and Cukierman E: Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer. Trends Biotechnol. 33:230–236. 2015. View Article : Google Scholar : PubMed/NCBI
26	Sun Y, Huang J and Yang Z: The roles of ADAMTS in angiogenesis and cancer. Tumour Biol. 36:4039–4051. 2015. View Article : Google Scholar : PubMed/NCBI
27	Martino-Echarri E, Fernández-Rodríguez R, Rodríguez-Baena FJ, Barrientos-Durán A, Torres-Collado AX, Plaza-Calonge Mdel C, Amador-Cubero S, Cortés J, Reynolds LE, Hodivala-Dilke KM, et al: Contribution of ADAMTS1 as a tumor suppressor gene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen-1 and nidogen-2. Int J Cancer. 133:2315–2324. 2013. View Article : Google Scholar : PubMed/NCBI
28	Ocak Z, Acar M, Gunduz E, Gunduz M, Demircan K, Uyeturk U and Ozlü T: Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells. Eur Rev Med Pharmacol Sci. 17:1185–1190. 2013.PubMed/NCBI
29	Fontanil T, Rúa S, Llamazares M, Moncada-Pazos A, Quirós PM, García-Suárez O, Vega JA, Sasaki T, Mohamedi Y, Esteban MM, et al: Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells. Oncotarget. 5:1253–1264. 2014. View Article : Google Scholar : PubMed/NCBI
30	Guo X, Li J, Zhang H, Liu H, Liu Z and Wei X: Relationship between ADAMTS8, ADAMTS18, and ADAMTS20 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) expressions and tumor molecular classification, clinical pathological parameters, and prognosis in breast invasive ductal carcinoma. Med Sci Monit. 24:3726–3735. 2018. View Article : Google Scholar : PubMed/NCBI
31	Held-Feindt J, Paredes EB, Blömer U, Seidenbecher C, Stark AM, Mehdorn HM and Mentlein R: Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas. Int J Cancer. 118:55–61. 2006. View Article : Google Scholar : PubMed/NCBI
32	Ishikawa N, Daigo Y, Yasui W, Inai K, Nishimura H, Tsuchiya E, Kohno N and Nakamura Y: ADAM8 as a novel serological and histochemical marker for lung cancer. Clin Cancer Res. 10:8363–8370. 2004. View Article : Google Scholar : PubMed/NCBI
33	Ko SY, Lin SC, Wong YK, Liu CJ, Chang KW and Liu TY: Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma. Cancer Lett. 245:33–43. 2007. View Article : Google Scholar : PubMed/NCBI
34	Lendeckel U, Kohl J, Arndt M, Carl-McGrath S, Donat H and Röcken C: Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. J Cancer Res Clin Oncol. 131:41–48. 2005. View Article : Google Scholar : PubMed/NCBI
35	Kilic MO, Aynekin B, Kara A, Icen D and Demircan K: Differentially regulated ADAMTS1, 8, and 18 in gastric adenocarcinoma. Bratisl Lek Listy. 118:71–76. 2017.PubMed/NCBI