Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2013, vol. 22, nr 6, November-December, p. 839–845

Publication type: original article

Language: English

The Clinical and Prognostic Significance of CCN3 Expression in Patients with Cervical Cancer

Znaczenie kliniczne i prognostyczne ekspresji CCN3 u pacjentek chorych na raka szyjki macicy

Ting Zhang1,B,D, Chun Zhao2,B, Liang Luo3,4,C, Jingying Xiang1,E, Qingmin Sun1,D, Jing Cheng1,C, Daozhen Chen1,A,F

1 Wuxi Maternity and Child Health Hospital, Nanjing Medical University, China

2 State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, China

3 Department of Respiratory Medicine, Jinling Hospital, Nanjing University Medical School, China

4 Wuxi Second Hospital, Nanjing Medical University, China


Background. CCN3 plays important roles in growth, differentiation, angiogenesis and adhesion. Recently, the role of CCN3 in human carcinogenesis has become an area of great interest. However, little is known about the function of CCN3 in human cervical cancer.
Objectives. The aim of this study was to investigate the expression profile of CCN3 in cervical cancer and to assess its clinical significance.
Material and Methods. In this study, qRT-PCR, immunohistochemistry and Western blotting analysis were used in the detection of CCN3 mRNA and protein expression, both in cervical cancer and in corresponding normal tissue, respectively. The data was correlated with clinicopathological features. A survival analysis was performed to assess the prognostic significance.
Results. CCN3 mRNA was overexpressed in cervical cancer tissue when compared with corresponding normal tissue, as was CCN3 protein. Upregulation of CCN3 was significantly associated with the stage of the disease (P = 0.017) and with lymph node involvement (P = 0.006). Using the Kaplan-Meier analysis, a comparison of survival curves of low vs. high expressers of CCN3 revealed a highly significant difference in human cervical cancer tissue (P = 0.021), which suggests that overexpression of CCN3 is associated with a poorer prognosis.
Conclusion. The results of the current study suggest that CCN3 may play an important role in cervical carcinogenesis and therefore may have potential as a biomarker for prognosis and as a therapeutic target in cervical cancer

Key words

CCN3; cervical cancer; clinicopathological parameters; prognosis.

References (19)

  1. Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, Naghavi M: Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet 2011, 378, 1461–1484.
  2. Chen PC, Lin TH, Cheng HC, Tang CH: CCN3 increases cell motility and ICAM-1 expression in prostate cancer cells. Carcinogenesis 2012, 33, 937–945.
  3. Planque N, Perbal B: A structural approach to the role of CCN (CYR61/CTgF/NoV) proteins in tumourigenesis. Cancer Cell Int 2003, 3, 15.
  4. Zhang Y, Wang C: Nephroblastoma overexpressed (NoV/CCN3) gene: a paired-domain-specific PAX3-FKHR transcription target that promotes survival and motility in alveolar rhabdomyosarcoma cells. oncogene 2011, 30, 3549–3562.
  5. Huang CY, Lee CY, Chen MY, Tsai HC, Hsu HC, Tang CH: Nephroblastoma overexpressed gene (NoV) enhances cell motility and CoX-2 upregulation of human osteosarcoma involves αvβ5 integrin, ILK and AP-1-dependent pathways. Biochem Pharmacol 2011, 81, 577–585.
  6. Benini S, Perbal B, Zambelli D, Colombo MP, Manara MC, Serra M, Parenza M, Martinez V, Picci P, Scotlandi K: In Ewing’s sarcoma CCN3(NoV) inhibits proliferation while promoting migration and invasion of the same cell type. oncogene 2005, 24, 4349–4361.
  7. Tzeng HE, Chen JC, Tsai CH, Kuo CC, Hsu HC, Hwang WL, Fong YC, Tang CH: CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway. J Cell Physiol 2011, 226, 3181–3189.
  8. Wang N, Ma Q, Wang Y, Ma G, Zhai H: CacyBP/SIP expression is involved in the clinical progression of breast cancer. World J Surg 2010, 34, 2545–2552,
  9. Imesch P, Fink D: Cervical cancer. Ther Umsch 2011, 68, 545–552.
  10. Holbourn KP, Acharva KR, Perbal B: The CCN family of proteins: structure-function relationships. Trends Biochem Sci 2008, 33, 461–473.
  11. Perbal B: NoV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues. Mol Pathol 2001, 54, 57–79.
  12. Perbal B: CCN proteins: multifunctional signalling regulators. Lancet 2004, 363, 62–64.
  13. Lin CG, Leu SJ, Chen N, Tebeau CM, Lin SX, Yeung CY, Lau LF: CCN3 (NoV) is a novel angiogenic regulator of the CCN protein family. J Biol Chem 2003, 278, 24200–24208.
  14. Lin CG, Chen CC, Leu SJ, Grzeszkiewicz TM, Lau LF: Integrin-dependent functions of the angiogenic inducer NoV (CCN3): implication in wound healing. J Biol Chem 2005, 280, 8229–8237.
  15. Chen CC, Lau LF: Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol 2009, 41, 771–783.
  16. Perbal B, Zuntini M, Zambelli D, Lopez-Guerrero JA, Llombart-Bosch A, Scotlandi K, Picci P: Prognostic value of CCN3 in osteosarcoma. Clin Cancer Res 2008, 14, 701–709.
  17. Vallacchi V, Daniotti M, Ratti F, Di Stasi D, Deho P, De Filippo A, Tragni G, Balsari A, Carbone A, Rivoltini L, Parmiani G, Lazar N, Perbal B, Rodolfo M: CCN3/nephroblastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma. Cancer Res 2008, 68, 715–723.
  18. Maillard M, Cadot B, Ball RY, Sethia K, Edwards DR, Perbal B, Tatoud R: Differential expression of the ccn3 (nov) protooncogene in human prostate cell lines and tissues. Mol Pathol 2001, 54, 275–280.
  19. Ouellet V, Tiedemann K, Mourskaia A, Fong JE, Tran-Thanh D, Amir E, Clemons M, Perbal B, Komarova SV, Siegel PM: CCN3 impairs osteoblast and stimulates osteoclast differentiation to favor breast cancer metastasis to bone. Am J Pathol 2011, 178, 2377–2388.