Expression and clinical significance of Apollon in esophageal squamous cell carcinoma

Li,Rong; Chen,Bo‑Lin; Zhou,Yan‑Wu; Guo,Ren‑Wei; Shuai,Meng‑Ting; Zeng,Jun‑Xian; Leng,Ai‑Min

doi:10.3892/mmr.2016.5473

Expression and clinical significance of Apollon in esophageal squamous cell carcinoma

Authors:
- Rong Li
- Bo‑Lin Chen
- Yan‑Wu Zhou
- Ren‑Wei Guo
- Meng‑Ting Shuai
- Jun‑Xian Zeng
- Ai‑Min Leng
View Affiliations

Affiliations: Department of Gastroenterology, Xiangya Hospital, Changsha, Hunan 410008, P.R. China, Thoracic Medicine Department II, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South Univerisity, Changsha, Hunan 410013, P.R. China, Department of Thoracic Surgery, Xiangya Hospital, Central South Univerisity, Changsha, Hunan 410008, P.R. China, Department of Clinical Medicine, Hunan Xiangnan College, Chenzhou, Hunan 423043, P.R. China
Published online on: July 6, 2016 https://doi.org/10.3892/mmr.2016.5473
Pages: 1933-1940
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Apollon, an unusually large member of the inhibitors of apoptosis protein family, may be important for oncogenesis development. The aim of the present study was to assess the association between esophageal squamous cell carcinoma (ESCC) and Apollon expression levels, and to highlight the association between Apollon and the occurrence, development and prognosis of ESCC. Apollon expression was detected by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction in ESCC tissues, adjacent non‑cancerous tissues and paired normal tissues respectively, in order to analyze the association between Apollon expression and the clinicopathological features of ESCC. Survival analysis was used to assess the prognostic significance of Apollon expression. It was determined that the mRNA and protein expression levels of Apollon were significantly higher in the carcinoma tissues compared with the adjacent non‑cancerous tissues and normal control tissues (P<0.001). There was a significant difference in lymph node involvement and the tumor, nodes, and metastases stage in patients categorized according to different Apollon expression levels. The prognostic significance of Apollon was also determined using the log‑rank method. The overexpression of Apollon was associated with shorter overall survival and disease-free survival rates. The present study indicates that Apollon expression is associated with the biological characteristics of ESCC, and may be a valuable prognostic factor and a novel chemotherapeutic target for ESCC treatment.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Mariette C, Piessen G and Triboulet JP: Therapeutic strategies in oesophageal carcinoma: Role of surgery and other modalities. Lancet Oncol. 8:545–553. 2007. View Article : Google Scholar : PubMed/NCBI
3	Lerut T, Coosemans W, Decker G, De Leyn P, Nafteux P and Van Raemdonck D: Cancer of the esophagus and gastroesophageal junction: Potentially curative therapies. Surg Oncol. 10:113–122. 2001. View Article : Google Scholar : PubMed/NCBI
4	Giancotti FG and Tarone G: Positional control of cell fate through joint integrin/receptor protein kinase signaling. Annu Rev Cell Dev Biol. 19:173–206. 2003. View Article : Google Scholar : PubMed/NCBI
5	Naito M: Molecular mechanism of apoptosis inhibition by IAPs and its implication to cancer therapy. Seikagaku. 78:525–528. 2006.In Japanese. PubMed/NCBI
6	Evan G: Cancer - a matter of life and cell death. Int J Cancer. 71:709–711. 1997. View Article : Google Scholar : PubMed/NCBI
7	Srinivasula SM and Ashwell JD: IAPs: what's in a name? Mol Cell. 30:123–135. 2008. View Article : Google Scholar : PubMed/NCBI
8	Wong RS: Apoptosis in cancer: From pathogenesis to treatment. J Exp Clin Cancer Res. 30:872011. View Article : Google Scholar : PubMed/NCBI
9	Hauser HP, Bardroff M, Pyrowolakis G and Jentsch S: A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. J Cell Biol. 141:1415–1422. 1998. View Article : Google Scholar : PubMed/NCBI
10	Chen Z, Naito M, Hori S, Mashima T, Yamori T and Tsuruo T: A human IAP-family gene, apollon, expressed in human brain cancer cells. Biochem Biophys Res Commun. 264:847–854. 1999. View Article : Google Scholar : PubMed/NCBI
11	Qiu XB and Goldberg AL: The membrane-associated inhibitor of apoptosis protein, BRUCE/Apollon, antagonizes both the precursor and mature forms of Smac and caspase-9. J Biol Chem. 280:174–182. 2005. View Article : Google Scholar
12	Qiu XB, Markant SL, Yuan J and Goldberg AL: Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis. EMBO J. 23:800–810. 2004. View Article : Google Scholar : PubMed/NCBI
13	Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, Katayama R, Hashimoto C, Zhang X, Noda T, et al: Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol. 6:849–860. 2004. View Article : Google Scholar : PubMed/NCBI
14	Lamers F, Schild L, Koster J, Speleman F, Øra I, Westerhout EM, van Sluis P, Versteeg R, Caron HN and Molenaar JJ: Identification of BIRC6 as a novel intervention target for neuroblastoma therapy. BMC Cancer. 12:2852012. View Article : Google Scholar : PubMed/NCBI
15	Bianchini M, Levy E, Zucchini C, Pinski V, Macagno C, De Sanctis P, Valvassori L, Carinci P and Mordoh J: Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa. Int J Oncol. 29:83–94. 2006.PubMed/NCBI
16	Low CG, Luk IS, Lin D, Fazli L, Yang K, Xu Y, Gleave M, Gout PW and Wang Y: BIRC6 protein, an inhibitor of apoptosis: Role in survival of human prostate cancer cells. PloS One. 8:e558372013. View Article : Google Scholar : PubMed/NCBI
17	Pohl C and Jentsch S: Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell. 132:832–845. 2008. View Article : Google Scholar : PubMed/NCBI
18	Ren J, Shi M, Liu R, Yang QH, Johnson T, Skarnes WC and Du C: The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development. Proc Natl Acad Sci USA. 102:565–570. 2005. View Article : Google Scholar : PubMed/NCBI
19	Chu L, Gu J, Sun L, Qian Q, Qian C and Liu X: Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil. Gene Ther. 15:484–494. 2008. View Article : Google Scholar : PubMed/NCBI
20	Lopergolo A, Pennati M, Gandellini P, Orlotti NI, Poma P, Daidone MG, Folini M and Zaffaroni N: Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation. Br J Cancer. 100:739–746. 2009. View Article : Google Scholar : PubMed/NCBI
21	Van Houdt WJ, Emmink BL, Pham TV, Piersma SR, Verheem A, Vries RG, Fratantoni SA, Pronk A, Clevers H, Borel Rinkes IH, et al: Comparative proteomics of colon cancer stem cells and differentiated tumor cells identifies BIRC6 as a potential therapeutic target. Mol Cell Proteomics. 10:M111.0113532011. View Article : Google Scholar : PubMed/NCBI
22	Chen Y, Fu D, Xi J, Ji Z, Liu T, Ma Y, Zhao Y, Dong L, Wang Q and Shen X: Expression and clinical significance of UCH37 in human esophageal squamous cell carcinoma. Dig Dis Sci. 57:2310–2317. 2012. View Article : Google Scholar : PubMed/NCBI
23	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
24	Sobin LH, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumors. 7th ed. Oxford: Wiley-Blackwell; 2010
25	Zhang S, Tang W, Weng S, Liu X, Rao B, Gu J, Chen S, Wang Q, Shen X, Xue R and Dong L: Apollon modulates chemosensitivity in human esophageal squamous cell carcinoma. Oncotarget. 5:7183–7197. 2014. View Article : Google Scholar : PubMed/NCBI
26	Wang L, Chen YJ, Hou J, Wang YY, Tang WQ, Shen XZ and Tu RQ: Expression and clinical significance of BIRC6 in human epithelial ovarian cancer. Tumour Biol. 35:4891–4896. 2014. View Article : Google Scholar : PubMed/NCBI
27	Sung KW, Choi J, Hwang YK, Lee SJ, Kim HJ, Lee SH, Yoo KH, Jung HL and Koo HH: Overexpression of Apollon, an anti-apoptotic protein, is associated with poor prognosis in childhood de novo acute myeloid leukemia. Clin Cancer Res. 13:5109–5114. 2007. View Article : Google Scholar : PubMed/NCBI
28	Ismail EA, Mahmoud HM, Tawfik LM, Habashy DM, Adly AA, El-Sherif NH and Abdelwahab MA: BIRC6/Apollon gene expression in childhood acute leukemia: Impact on therapeutic response and prognosis. Eur J Haematol. 88:118–127. 2012. View Article : Google Scholar
29	Tang W, Xue R, Weng S, Wu J, Fang Y, Wang Y, Ji L, Hu T, Liu T, Huang X, et al: BIRC6 promotes hepatocellular carcinogenesis: Interaction of BIRC6 with p53 facilitating p53 degradation. Int J Cancer. 136:E475–E487. 2015. View Article : Google Scholar
30	Dong X, Lin D, Low C, Vucic EA, English JC, Yee J, Murray N, Lam WL, Ling V, Lam S, et al: Elevated expression of BIRC6 protein in non-small-cell lung cancers is associated with cancer recurrence and chemoresistance. J Thorac Oncol. 8:161–170. 2013. View Article : Google Scholar : PubMed/NCBI
31	Abe S, Yamamoto K, Hasegawa M, Inoue M, Kurata M, Hirokawa K, Kitagawa M, Nakagawa Y and Suzuki K: Bone marrow cells of myelodysplastic syndromes exhibit significant expression of apollon, livin and ILP-2 with reduction after transformation to overt leukemia. Leuk Res. 29:1095–1096. 2005. View Article : Google Scholar : PubMed/NCBI
32	Tassi E, Zanon M, Vegetti C, Molla A, Bersani I, Perotti V, Pennati M, Zaffaroni N, Milella M, Ferrone S, et al: Role of Apollon in human melanoma resistance to antitumor agents that activate the intrinsic or the extrinsic apoptosis pathways. Clin Cancer Res. 18:3316–3327. 2012. View Article : Google Scholar : PubMed/NCBI
33	Nemoto T, Kitagawa M, Hasegawa M, Ikeda S, Akashi T, Takizawa T, Hirokawa K and Koike M: Expression of IAP family proteins in esophageal cancer. Exp Mol Pathol. 76:253–259. 2004. View Article : Google Scholar : PubMed/NCBI
34	Zhou S, Ye W, Shao Q, Qi Y, Zhang M and Liang J: Prognostic significance of XIAP and NF-κB expression in esophageal carcinoma with postoperative radiotherapy. World J Surg Oncol. 11:2882013. View Article : Google Scholar
35	Vaĭshlia NA, Zinov'eva MV, Sass AV, Kopantsev EP, Vinogradova TV and Sverdlov ED: Increase of BIRC5 gene expression in non-small cell lung cancer and esophageal squamous cell carcinoma does not correlate with expression of genes SMAC/DIABLO and PML encoding its inhibitors. Mol Biol (Mosk). 42:652–661. 2008.