Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

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

Authors: Yi Li, Hui Guo, Danfeng Dong, Huili Wu, Enxiao Li

Published in: Diagnostic Pathology | Issue 1/2013

Login to get access

Abstract

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.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​1166551968105508​.
Appendix
Available only for authorised users
Literature
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.CrossRef
2.
Umar S, Fleischer DE: Esophageal cancer: epidemiology, pathogenesis and prevention. Nat Clin Pract Gastroenterol Hepatol. 2008, 5: 517-526. 10.1038/ncpgasthep1223.CrossRef
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. 10.1073/pnas.89.8.3511.PubMedCentralCrossRefPubMed
4.
Franke EK, Yuan HE, Luban J: Specific incorporation of cyclophilin A into HIV-1 virions. Nature. 1994, 372: 359-362. 10.1038/372359a0.CrossRefPubMed
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. 10.1161/01.RES.87.9.789.CrossRefPubMed
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.PubMedCentralCrossRefPubMed
7.
Lee J, Kim SS: An overview of cyclophilins in human cancers. J Int Med Res. 2010, 38: 1561-1574. 10.1177/147323001003800501.CrossRefPubMed
8.
Howard BA, Zheng Z, Campa MJ, Wang MZ, Sharma A, Haura E, Herndon JE, Fitzgerald MC, Bepler G, Patz EF: 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. 10.1016/j.lungcan.2004.05.013.CrossRefPubMed
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. 10.1158/1055-9965.EPI-06-0216.CrossRefPubMed
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. 10.1002/cncr.21862.CrossRefPubMed
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. 10.1021/pr020006i.CrossRefPubMed
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. 10.1002/jcb.21727.CrossRefPubMed
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. 10.1021/pr800174k.CrossRefPubMed
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. 10.1016/j.ajpath.2012.08.044.PubMedCentralCrossRefPubMed
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. 10.1007/s00432-003-0500-4.CrossRefPubMed
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. 10.1016/S0304-3835(98)00241-9.CrossRefPubMed
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.PubMed
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. 10.1007/s11010-008-9896-0.CrossRefPubMed
19.
Kessenbrock K, Plaks V, Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010, 141: 52-67. 10.1016/j.cell.2010.03.015.PubMedCentralCrossRefPubMed
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. 10.1095/biolreprod.107.063743.PubMedCentralCrossRefPubMed
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. 10.1007/s11010-011-0909-z.CrossRefPubMed
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: 442-10.1186/1471-2407-12-442.PubMedCentralCrossRefPubMed
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: 305-10.1186/1471-2407-13-305.PubMedCentralCrossRefPubMed
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: 141-10.1186/1477-7819-11-141.PubMedCentralCrossRefPubMed
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: 47-10.1186/1746-1596-8-47.PubMedCentralCrossRefPubMed
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: 177-10.1186/1746-1596-8-177.PubMedCentralCrossRefPubMed
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. 10.1074/mcp.M700544-MCP200.CrossRefPubMed
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. 10.4161/cbt.11.5.14678.CrossRefPubMed
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. 10.1111/j.1601-0825.2010.01730.x.CrossRefPubMed
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. 10.1039/c2mb25286d.CrossRefPubMed
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. 10.1111/j.1365-2559.2011.04130.x.CrossRefPubMed
Metadata
Title
Expression and prognostic relevance of Cyclophilin A and matrix metalloproteinase 9 in esophageal squamous cell carcinoma
Authors
Yi Li
Hui Guo
Danfeng Dong
Huili Wu
Enxiao Li
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-207

Other articles of this Issue 1/2013

Diagnostic Pathology 1/2013 Go to the issue

Case Report

Mediastinal epithelioid hemangioendothelioma with abundant spindle cells and osteoclast-like giant cells mimicking malignant fibrous histiocytoma

Research

Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population

Case Report

Lymphoepithelioma-like carcinoma of the stomach: a case report and review of the literature

Case Report

Sclerosing rhabdomyosarcoma presenting in the masseter muscle: a case report

Letter to the Editor

Benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma arising from the nose

Research

High frequency distribution of heterogeneous vancomycin resistant Enterococcous faecium (VREfm) in Iranian hospitals