Expression and prognostic relevance of Cyclophilin A and matrix metalloproteinase 9 in esophageal squamous cell carcinoma

Diagnostic Pathology

Enxiao Li¹  Huili Wu¹  Danfeng Dong¹  Hui Guo¹  Yi Li¹ 

[1] Department of Oncology, First Affiliated Hospital, Medical School, Xi’an Jiaotong University, Yanta West Road No. 277, Xi’an 710061, Shaanxi Province, China

关键词: Matrix metalloproteinase 9;    Cyclophilin A;    Esophageal squamous cell carcinoma;   

Others  :  803806
DOI  :  10.1186/1746-1596-8-207

 received in 2013-08-12, accepted in 2013-12-06,  发布年份 2013

【 摘 要 】

Aims

To guide clinicians in selecting treatment options for esophageal squamous cell carcinoma (ESCC) patients, reliable markers predictive of clinical outcome are desirable. This study analyzed the correlation of cyclophilin A (CypA) and matrix metalloproteinase 9 (MMP9) in ESCC and their relationships to clinicopathological features and survival.

Methods

We immunohistochemically investigated 70 specimens of ESCC tissues using CypA and MMP9 antibodies. Then, the correlations between CypA and MMP9 expression and clinicopathological features and its prognostic relevance were determined.

Results

Significant correlations were only found in high level of CypA and MMP9 expression with tumor differentiation and lymph node status. Significant positive correlations were found between the expression status of CypA and that of MMP9. Overexpression of CypA and metastasis were significantly associated with shorter progression free survival times in univariate analysis. Multivariate analysis confirmed that CypA expression was an independent prognostic factor.

Conclusions

CypA might be correlated with the differentiation, and its elevated expression may be an adverse prognostic indicator for the patients of ESCC. CypA/MMP9 signal pathway may be attributed to the malignant transformation of ESCC, and attention should be paid to a possible target for therapy.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1166551968105508 webcite.

【 授权许可】

   
2013 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Parkin DM, Bray FI, Devesa SS: Cancer burden in the year 2000. The global picture. Eur J Cancer 2001, 2001(37 Suppl 8):S4-S66.
• [2]Umar S, Fleischer DE: Esophageal cancer: epidemiology, pathogenesis and prevention. Nat Clin Pract Gastroenterol Hepatol 2008, 5:517-526.
• [3]Sherry B, Yarlett N, Strupp A, Cerami A: Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages. Proc Natl Acad Sci U S A 1992, 89:3511-3515.
• [4]Franke EK, Yuan HE, Luban J: Specific incorporation of cyclophilin A into HIV-1 virions. Nature 1994, 372:359-362.
• [5]Jin ZG, Melaragno MG, Liao DF, Yan C, Haendeler J, Suh YA, Lambeth JD, Berk BC: Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res 2000, 87:789-796.
• [6]Gwinn WM, Damsker JM, Falahati R, Okwumabua I, Kelly-Welch A, Keegan AD, Vanpouille C, Lee JJ, Dent LA, Leitenberg D, Bukrinsky MI, Constant SL: Novel approach to inhibit asthma-mediated lung inflammation using anti-CD147 intervention. J Immunol 2006, 177:4870-4879.
• [7]Lee J, Kim SS: An overview of cyclophilins in human cancers. J Int Med Res 2010, 38:1561-1574.
• [8]Howard BA, Zheng Z, Campa MJ, Wang MZ, Sharma A, Haura E, Herndon JE 2nd, Fitzgerald MC, Bepler G, Patz EF Jr: Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer. Lung Cancer 2004, 46:313-323.
• [9]Lou J, Fatima N, Xiao Z, Stauffer S, Smythers G, Greenwald P, Ali IU: Proteomic profiling identifies cyclooxygenase-2-independent global proteomic changes by celecoxib in colorectal cancer cells. Cancer Epidemiol Biomarkers Prev 2006, 15:1598-1606.
• [10]Li M, Zhai Q, Bharadwaj U, Wang H, Li F, Fisher WE, Chen C, Yao Q: Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. Cancer 2006, 106:2284-2294.
• [11]Hathout Y, Riordan K, Gehrmann M, Fenselau C: Differential protein expression in the cytosol fraction of an MCF-7 breast cancer cell line selected for resistance toward melphalan. J Proteome Res 2002, 1:435-442.
• [12]Qi YJ, He QY, Ma YF, Du YW, Liu GC, Li YJ, Tsao GS, Ngai SM, Chiu JF: Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma. J Cell Biochem 2008, 104:1625-1635.
• [13]Al-Ghoul M, Brück TB, Lauer-Fields JL, Asirvatham VS, Zapata C, Kerr RG, Fields GB: Comparative proteomic analysis of matched primary and metastatic melanoma cell lines. J Proteome Res 2008, 7:4107-4118.
• [14]Shuman Moss LA, Jensen-Taubman S, Stetler-Stevenson WG: Matrix metalloproteinases: changing roles in tumor progression and metastasis. Am J Pathol 2012, 181:1895-1899.
• [15]Samantaray S, Sharma R, Chattopadhyaya TK, Gupta SD, Ralhan R: Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2004, 130:37-44.
• [16]Corton JC, Moreno ES, Merritt A, Bocos C, Cattley RC: Cloning genes responsive to a hepatocarcinogenic peroxisome proliferator chemical reveals novel targets of regulation. Cancer Lett 1998, 134(1):61-71.
• [17]Obchoei S, Wongkhan S, Wongkham C, Li M, Yao Q, Chen C: Cyclophilin A: potential functions and therapeutic target for human cancer. Med Sci Monit 2009, 15:RA221-RA232.
• [18]Calhoun CC, Lu YC, Song J, Chiu R: Knockdown endogenous CypA with siRNA in U2OS cells results in disruption of F-actin structure and alters tumor phenotype. Mol Cell Biochem 2009, 320:35-43.
• [19]Kessenbrock K, Plaks V, Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010, 141:52-67.
• [20]Lockwood CJ, Oner C, Uz YH, Kayisli UA, Huang SJ, Buchwalder LF, Murk W, Funai EF, Schatz F: Matrix metalloproteinase 9 (MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual cells. Biol Reprod 2008, 78(6):1064-1072.
• [21]Zhang M, Dai C, Zhu H, Chen S, Wu Y, Li Q, Zeng X, Wang W, Zuo J, Zhou M, Xia Z, Ji G, Saiyin H, Qin L, Yu L: Cyclophilin A promotes human hepatocellular carcinoma cell metastasis via regulation of MMP3 and MMP9. Mol Cell Biochem 2011, 357:387-395.
• [22]Qian Z, Zhao X, Jiang M, Jia W, Zhang C, Wang Y, Li B, Yue W: Downregulation of cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9. BMC Cancer 2012, 12:442. BioMed Central Full Text
• [23]Cao W, Yu G, Lu Q, Zhang J: Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous cell carcinoma correlates with a poor prognosis. BMC Cancer 2013, 13:305. BioMed Central Full Text
• [24]Zhang H, Chen W, Duan CJ, Zhang CF: Overexpression of HSPA2 is correlated with poor prognosis in esophageal squamous cell carcinoma. World J Surg Oncol 2013, 11:141. BioMed Central Full Text
• [25]Li M, Tang Y, Zang W, Xuan X, Wang N, Ma Y, Wang Y, Dong Z, Zhao G: Analysis of HAX-1 gene expression in esophageal squamous cell carcinoma. Diagn Pathol 2013, 8:47. BioMed Central Full Text
• [26]Peng J, Hu Q, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Wei W, Liu S, Wang H: USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma. Diagn Pathol 2013, 8:177. BioMed Central Full Text
• [27]Li Z, Zhao X, Bai S, Wang Z, Chen L, Wei Y, Huang C: Proteomics identification of cyclophilin a as a potential prognostic factor and therapeutic target in endometrial carcinoma. Mol Cell Proteomics 2008, 7:1810-1823.
• [28]Yang J, Li A, Yang Y, Li X: Identification of cyclophilin A as a potential prognostic factor for clear-cell renal cell carcinoma by comparative proteomic analysis. Cancer Biol Ther 2011, 11:535-546.
• [29]Huang CF, Sun ZJ, Zhao YF, Chen XM, Jia J, Zhang WF: Increased expression of peroxiredoxin 6 and cyclophilin A in squamous cell carcinoma of the tongue. Oral Dis 2011, 17:328-334.
• [30]Peng Y, Li X, Wu M, Yang J, Liu M, Zhang W, Xiang B, Wang X, Li X, Li G, Shen S: New prognosis biomarkers identified by dynamic proteomic analysis of colorectal cancer. Mol Biosyst 2012, 8:3077-3088.
• [31]Huang C, Sun Z, Sun Y, Chen X, Zhu X, Fan C, Liu B, Zhao Y, Zhang W: Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma. Histopathology 2012, 60:793-803.