January 2014, 31:764
Date: 21 Jan 2014
Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer patients
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The goal of this study was to determine the diagnostic and prognostic potential of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer. We analyzed a tissue microarray comprised of 100 breast cancer cases and 70 matched normal samples. Analysis of an online database, which included 2,977 patients, was also performed. There was a significant difference in cytoplasmic expression of XIAP (XIAP-C) between breast cancer tissue and matched normal (p < 0.001). Staining of XIAP-C was defined as negative (breast cancer 8.42 % vs. normal 30.91 %), slight (40.0 vs. 45.45 %), moderate (43.16 vs. 23.64 %), or high (8.42 vs. 0 %). High XIAP-C protein expression correlated with human epidermal growth factor receptor 2 (HER-2) status (p = 0.010) and with human p53 mutant-type (P53) status (p = 0.039). We found that XIAP expression did not correlate with disease-free survival (p = 0.706) and overall survival (p = 0.496) of breast cancer patients. An Internet-based system analysis confirmed our results. In the subgroup analysis, basal-like breast cancer patients with high XIAP levels in the tumor had a significantly increased risk of relapse; thus, the up-regulation of XIAP appeared to be predictive of poor relapse-free survival (p = 0.013). Kaplan–Meier curves also identified a significant correlation between distant metastasis-free survival and XIAP expression in patients with lymph-node-negative disease (p = 0.030). In summary, expression of XIAP-C was significantly higher in breast cancer compared to normal tissue. XIAP-C expression correlated with HER-2 status and may be considered a prognostic biomarker for basal-like breast cancer patients.
Chaoquan H, Huang L, Gest C, Xi X, Janin A, Soria C, Li H, He L. Opposite regulation by PI3 K/Akt and MAPK/ERK pathways of tissue factor expression, cell-associated procoagulant activity and invasiveness in MDA-MB-231 cells. J Hematol Oncol. 2012;5:16.CrossRef
Vaux DL, Silke J. Mammalian mitochondrial IAP binding proteins. Biochem Biophys Res Commun. 2003;3:499–504.CrossRef
Schimmer AD, Welsh K, Pinilla C, Wang Z, Krajewska M, Bonneau MJ, Pedersen IM, Kitada S, Scott FL, Bailly-Maitre B, Glinsky G, Scudiero D, Sausville E, Salvesen G, Nefzi A, Ostresh JM, Houghten RA, Reed JC. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell. 2004;1:25–35.CrossRef
Deveraux QL, Takahashi R, Salvesen GS, Reed JC. X-linked IAP is a direct inhibitor of cell-death proteases. Nature. 1997;6639:300–4.
Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J. 1998;8:2215–23.CrossRef
Mohapatra S, Chu B, Zhao X, Pledger WJ. Accumulation of p53 and reductions in XIAP abundance promote the apoptosis of prostate cancer cells. Cancer Res. 2005;65:7717–23.PubMed
Yang XH, Feng ZE, Yan M, Hanada S, Zuo H, Yang CZ, Han ZG, Guo W, Chen WT, Zhang P. XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer. PLoS One. 2012;3:e31601.CrossRef
Chen X, Wang T, Yang D, Wang J, Li X, He Z, Chen F, Che X, Song X. Expression of the IAP protein family acts cooperatively to predict prognosis in human bladder cancer patients. Oncol Lett. 2013;4:1278–84.
Shi YH, Ding WX, Zhou J, He JY, Xu Y, Gambotto AA, Rabinowich H, Fan J, Yin XM. Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence. Hepatology. 2008;2:497–507.CrossRef
Györffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, Szallasi Z. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat. 2010;3:725–31.CrossRef
Zhang Y, Wang Y, Gao W, Zhang R, Han X, Jia M, Guan W. Transfer of siRNA against XIAP induces apoptosis and reduces tumor cells growth potential in human breast cancer in vitro and in vivo. Breast Cancer Res Treat. 2006;3:267–77.CrossRef
Hu Y, Cherton-Horvat G, Dragowska V, Baird S, Korneluk RG, Durkin JP, Mayer LD, LaCasse EC. Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo. Clin Cancer Res. 2003;9:2826–36.PubMed
Zhang FC, Song SL, Ma Y, Tang L, Xu YC, Wang HX. Effect of fibroblasts on breast cancer cell mammosphere formation and the regulation of stem cell-related gene expression. Int J Mol Med. 2011;3:365–71.
Xu YC, Wang HX, Tang L, Ma Y, Zhang FC. A systematic review of vinorelbine for the treatment of breast cancer. Breast J. 2013;2:180–8.CrossRef
Wang HX, Zhang FC, Ye F, Ma Y, David YZ. The effect of coptis chinensis on the signaling network in the squamous carcinoma cells. Front Biosci. 2011;3:326–40.CrossRef
Zhang S, Ding F, Luo A, Chen A, Yu Z, Ren S, Liu Z, Zhang L. XIAP is highly expressed in esophageal cancer and its downregulation by RNAi sensitizes esophageal carcinoma cell lines to chemotherapeutics. Cancer Biol Ther. 2007;6:6973–80.
Sun H, Lu J, Liu L, Yi H, Qiu S, Yang CY, Deschamps JR, Wang S. Nonpeptidic and potent small-molecule inhibitors of cIAP-1/2 and XIAP proteins. J Med Chem. 2010;17:6361–7.CrossRef
Amantana A, Lon don CA, Iversen PL, Devi GR. X-linked inhibitor of apoptosis protein inhibition induces apoptosis and enhances chemotherapy sensitivity in human prostate cancer cells. Mol Cancer Ther. 2004;3:699–707.PubMed
Ming L, Tao S, Zhen-fei Y, Yan-qun NA. XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder cancer. Chin Med J. 2007;6:469–73.
Arnt CR, Chiorean MV, Heldebrant MP, Gores GJ, Kaufmann SH. Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ. J Biol Chem. 2002;46:44236–43.CrossRef
Mizutani Y, Nakanishi H, Li YN, Matsubara H, Yamamoto K, Sato N, Shiraishi T, Nakamura T, Mikami K, Okihara K. Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis. Int J Oncol. 2007;30:919–25.PubMed
Che Y, Ye F, Xu R, Qing H, Wang X, Yin F, Cui M, Burstein D, Jiang B, Zhang DY. Co-expression of XIAP and cyclinD1 complex correlates with a poor prognosis in patients with hepatocellular carcinoma. Am J Pathol. 2012;5:1798–807.CrossRef
Yang L, Cao Z, Yan H, Wood WC. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy. Cancer Res. 2003;20:6815–24.
Jaffer S, Orta L, Sunkara S, Sabo E, Burstein DE. Immunohistochemical detection of antiapoptotic protein X-linked inhibitor of apoptosis in mammary carcinoma. Hum Pathol. 2007;6:864–70.CrossRef
Tenev T, Zachariou A, Wilson R, Ditzel M, Meier P. IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. Nat Cell Biol. 2005;1:70–7.CrossRef
Xiang G, Wen X, Wang H, Chen K, Liu H. Expression of X-linked inhibitor of apoptosis protein in human colorectal cancer and its correlation with prognosis. J Surg Oncol. 2009;8:708–12.
Kim MA, Lee HE, Lee HS, Yang HK, Kim WH. Expression of apoptosis-related proteins and its clinical implication in surgically resected gastric carcinoma. Virchows Arch. 2011;5:503–10.CrossRef
Aird KM, Ding X, Baras A, Wei J, Morse MA, Clay T, Lyerly HK, Devi GR. Trastuzumab signaling in ErbB2-overexpressing inflammatory breast cancer correlates with X-linked inhibitor of apoptosis protein expression. Mol Cancer Ther. 2008;1:38–47.CrossRef
- Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer patients
- Online Date
- January 2014
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- X-linked inhibitor of apoptosis
- Breast cancer
- Tissue microarray
- Industry Sectors
- Author Affiliations
- 1. Department of Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
- 3. Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
- 2. Department of Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China