Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer

Xu,Lihua; Peng,Sida; Huang,Qunai; Liu,Yu; Jiang,Hua; Li,Xi; Wang,Jiani

doi:10.3892/or.2016.5051

Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer

Authors:
- Lihua Xu
- Sida Peng
- Qunai Huang
- Yu Liu
- Hua Jiang
- Xi Li
- Jiani Wang
View Affiliations

Affiliations: Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510230, P.R. China, Breast Cancer Center, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: August 25, 2016 https://doi.org/10.3892/or.2016.5051
Pages: 1981-1988

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

Cyclase-associated protein 2 (CAP2) protein is reported to be upregulated in hepatocellular carcinoma (HCC). However, data regarding its expression pattern and clinical relevance in breast cancer are unknown. The aim of this study was to investigate CAP2 expression and its prognostic significance in breast cancer. CAP2 expression at the mRNA and protein levels was examined by real‑time quantitative-polymerase chain reaction and western blotting in 10 paired breast cancer tissues and adjacent normal tissues. The expression level of CAP2 protein in normal breast epithelial cells and breast cancer cell lines was quantified by western blotting. CAP2 protein expression was analyzed in paraffin‑embedded breast cancer samples, paired adjacent non‑tumor and normal breast tissues by immunohistochemical analysis. Statistical analyses were also performed to evaluate the clinicopathological significance of CAP2 expression. The results showed that the expression of CAP2 mRNA and protein was higher in breast cancer than that noted in the adjacent normal tissues in 10 paired samples. The expression level of CAP2 protein in breast cancer cell lines was higher than that in normal breast epithelial cells. In paraffin‑embedded tissue samples, the expression of CAP2 was higher in breast cancer than that found in the adjacent non‑cancerous tissues and normal breast tissues. Compared with the adjacent non‑cancerous tissues, overexpression of CAP2 was detected in 29.4% (37/126) of the patients. Overexpression of CAP2 was significantly associated with progesterone receptor (PR) expression (p<0.05), and decreased overall survival (OS) (p<0.05). In multivariate analysis, expression of CAP2 was an independent prognostic factor for OS [hazard ratio (HR), 4.821; 95% confidence interval (CI), 2.442‑9.518; p<0.001]. CAP2 is upregulated in breast cancer and is associated with the expression of PR and patient survival. CAP2 may serve as a prognostic indicator for patients with breast cancer.

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	Makkonen M, Bertling E, Chebotareva NA, Baum J and Lappalainen P: Mammalian and malaria parasite cyclase-associated proteins catalyze nucleotide exchange on G-actin through a conserved mechanism. J Biol Chem. 288:984–994. 2013. View Article : Google Scholar :
3	Fedor-Chaiken M, Deschenes RJ and Broach JR: SRV2, a gene required for RAS activation of adenylate cyclase in yeast. Cell. 61:329–340. 1990. View Article : Google Scholar : PubMed/NCBI
4	Olson MF and Sahai E: The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis. 26:273–287. 2009. View Article : Google Scholar
5	Yilmaz M and Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 28:15–33. 2009. View Article : Google Scholar : PubMed/NCBI
6	Peche V, Shekar S, Leichter M, Korte H, Schröder R, Schleicher M, Holak TA, Clemen CS, Ramanath-Y B, Pfitzer G, et al: CAP2, cyclase-associated protein 2, is a dual compartment protein. Cell Mol Life Sci. 64:2702–2715. 2007. View Article : Google Scholar : PubMed/NCBI
7	Liu Y, Cui X, Hu B, Lu C, Huang X, Cai J, He S, Lv L, Cong X, Liu G, et al: Upregulated expression of CAP1 is associated with tumor migration and metastasis in hepatocellular carcinoma. Pathol Res Pract. 210:169–175. 2014. View Article : Google Scholar
8	Yu XF, Ni QC, Chen JP, Xu JF, Jiang Y, Yang SY, Ma J, Gu XL, Wang H and Wang YY: Knocking down the expression of adenylate cyclase-associated protein 1 inhibits the proliferation and migration of breast cancer cells. Exp Mol Pathol. 96:188–194. 2014. View Article : Google Scholar : PubMed/NCBI
9	Hua M, Yan S, Deng Y, Xi Q, Liu R, Yang S, Liu J, Tang C, Wang Y and Zhong J: CAP1 is overexpressed in human epithelial ovarian cancer and promotes cell proliferation. Int J Mol Med. 35:941–949. 2015.PubMed/NCBI
10	Shibata R, Mori T, Du W, Chuma M, Gotoh M, Shimazu M, Ueda M, Hirohashi S and Sakamoto M: Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis. Clin Cancer Res. 12:5363–5368. 2006. View Article : Google Scholar : PubMed/NCBI
11	Masugi Y, Tanese K, Emoto K, Yamazaki K, Effendi K, Funakoshi T, Mori M and Sakamoto M: Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma. Pathol Int. 65:627–634. 2015. View Article : Google Scholar : PubMed/NCBI
12	Song LB, Zeng MS, Liao WT, Zhang L, Mo HY, Liu WL, Shao JY, Wu QL, Li MZ, Xia YF, et al: Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res. 66:6225–6232. 2006. View Article : Google Scholar : PubMed/NCBI
13	Ono S: The role of cyclase-associated protein in regulating actin filament dynamics - more than a monomer-sequestration factor. J Cell Sci. 126:3249–3258. 2013. View Article : Google Scholar : PubMed/NCBI
14	Bertling E, Hotulainen P, Mattila PK, Matilainen T, Salminen M and Lappalainen P: Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells. Mol Biol Cell. 15:2324–2334. 2004. View Article : Google Scholar : PubMed/NCBI
15	Yamazaki K, Takamura M, Masugi Y, Mori T, Du W, Hibi T, Hiraoka N, Ohta T, Ohki M, Hirohashi S, et al: Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. Lab Invest. 89:425–432. 2009. View Article : Google Scholar : PubMed/NCBI
16	Li M, Yang X, Shi H, Ren H, Chen X, Zhang S, Zhu J and Zhang J: Downregulated expression of the cyclase-associated protein 1 (CAP1) reduces migration in esophageal squamous cell carcinoma. Jpn J Clin Oncol. 43:856–864. 2013. View Article : Google Scholar : PubMed/NCBI
17	Xie SS, Tan M, Lin HY, Xu L, Shen CX, Yuan Q, Song XL and Wang CH: Overexpression of adenylate cyclase-associated protein 1 may predict brain metastasis in non-small cell lung cancer. Oncol Rep. 33:363–371. 2015.
18	Effendi K, Yamazaki K, Mori T, Masugi Y, Makino S and Sakamoto M: Involvement of hepatocellular carcinoma biomarker, cyclase-associated protein 2 in zebrafish body development and cancer progression. Exp Cell Res. 319:35–44. 2013. View Article : Google Scholar
19	Kirfel G, Rigort A, Borm B and Herzog V: Cell migration: Mechanisms of rear detachment and the formation of migration tracks. Eur J Cell Biol. 83:717–724. 2004. View Article : Google Scholar
20	Zhou GL, Zhang H and Field J: Mammalian CAP (Cyclase-associated protein) in the world of cell migration: Roles in actin filament dynamics and beyond. Cell Adhes Migr. 8:55–59. 2014. View Article : Google Scholar
21	Fu J, Li M, Wu DC, Liu LL, Chen SL and Yun JP: Increased expression of CAP2 indicates poor prognosis in hepatocellular carcinoma. Transl Oncol. 8:400–406. 2015. View Article : Google Scholar : PubMed/NCBI