Molecular Neurobiology

, Volume 53, Issue 9, pp 6209–6217 | Cite as

Proliferating Cell Nuclear Antigen Has an Association with Prognosis and Risks Factors of Cancer Patients: a Systematic Review

  • Qiongying Lv
  • Juan Zhang
  • Yuexiong Yi
  • Yue Huang
  • Yong Wang
  • Yijun Wang
  • Wei Zhang
Article
First Online:
Received:
Accepted:

Abstract

Proliferating cell nuclear antigen (PCNA) is reported as a famous marker in various tumors. A couple of articles have been published about the clinical function of PCNA on cancer progression; however, these results are conflicting in some degree. Thus, it is crucial to perform a systematic review and meta-analysis to identify their real actions. Here, we took cervical cancer and glioma as example and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (95 % CIs). In the present study, the PCNA expression in cervical cancer and gliomas patients was both correlated with 5-year-overall survival (OS) (HR = 4.41, 95 % CI 2.71–7.17, p = 0.000; HR = 4.40, 95 % CI 3.00–6.47, p = 0.000; respectively). In addition, a fixed effect model revealed a significant association between PCNA and FIGO stage (OR = 4.48, 95 % CI 3.48–5.77, p = 0.000) or WHO grade (OR = 5.64, 95 % CI 4.15–7.68, p = 0.000), rather than age (OR = 1.01, 95 % CI 0.71–1.43, p = 0.957; OR = 1.00, 95 % CI 0.80–1.24, p = 0.989; respectively). No heterogeneity was observed across all studies. According to funnel plot, no publication bias was reported. In conclusion, our systematic review suggests that PCNA expression is significantly associated with poor 5-year survival, advanced stage or higher WHO grade, which might be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target in cervical cancer, gliomas, or even more cancers.

Keywords

PCNA Prognosis Diagnosis Systematic review 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

We greatly thank other members in our lab for valuable suggestions and writing.

Compliance with Ethical Standards

Conflict of Interest

The authors state that there are no conflicts of interest to disclose.

References

  1. 1.
    Chiang CP, Lang MJ, Liu BY, Wang LJS, Hahn LJ, Kuo MYP (2000) Expression of proliferating cell nuclear antigen (PCNA) in oral submucous fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan. Oral Oncol 36(4):353–359CrossRefPubMedGoogle Scholar
  2. 2.
    Srinivasan M, Jewell SD (2001) Quantitative estimation of PCNA, c-myc, EGFR and TGF-alfa in oral submucous fibrosis—an immmunohistochemical study. Oral Oncol 37:461–467CrossRefPubMedGoogle Scholar
  3. 3.
    Huang WY, Coltrera M, Schubert M, Morton T, Truelove E, Wash S (1994) Histological evaluation of proliferating cell nuclrear antigen (PC 10) in oral epithelial hyperplasia and premalignanat lesions. Oral Surg Med Oral Patho Oral Radiol Endod 78:748–754CrossRefGoogle Scholar
  4. 4.
    Tsai ST, Jin YT (1995) Proliferating cell nuclear antigen (PCNA) expression in oral squamous cell carcinomas. J Oral Pathol Med 24(7):313–315CrossRefPubMedGoogle Scholar
  5. 5.
    Tsuji T, Sasaki K, Kimura Y, Yamada K, Mori M, Shinozaki F (1992) Measurement of proliferating cell nuclear antigen (PCNA) and its clinical application in oral cancers. Int J Oral Maxillofac Surg 21(6):369–372CrossRefPubMedGoogle Scholar
  6. 6.
    Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37(Suppl 8):S4–S66CrossRefPubMedGoogle Scholar
  7. 7.
    Zhang J, Zhu D, Lv Q, Yi Y, Li F, Zhang W (2015) The key role of astrocyte elevated gene-1 in CCR6-induced EMT in cervical cancer. Tumour BiolGoogle Scholar
  8. 8.
    Yan J, Zhang Y, Ren C, Shi W, Chen L (2015) Involvement of nuclear protein C23 in activation of EGFR signaling in cervical cancer. Tumour BiolGoogle Scholar
  9. 9.
    Dai C, Lv S, Shi R, Ding J, Zhong X, Song H, Ma X, Fan J et al (2015) Nuclear protein C23 on the cell surface plays an important role in activation of CXCR4 signaling in glioblastoma. Mol Neurobiol 52(3):1521–1526CrossRefPubMedGoogle Scholar
  10. 10.
    Yao C, Li P, Song H, Song F, Qu Y, Ma X, Shi R, Wu J (2015) CXCL12/CXCR4 axis upregulates twist to induce EMT in human glioblastoma. Mol NeurobiolGoogle Scholar
  11. 11.
    Yang X, Lv S, Zhou X, Liu Y, Li D, Shi R, Kang H, Zhang J et al (2015) The clinical implications of transforming growth factor beta in pathological grade and prognosis of glioma patients: a meta-analysis. Mol Neurobiol 52(1):270–276CrossRefPubMedGoogle Scholar
  12. 12.
    SONG J, PAN X, LI H, ZU Y, LI F, SONG J (1999) Expression of p53 protein and cellular proliferative activity in cervix carcinoma. J Fourth Mil Med Univ 20(2):1–5Google Scholar
  13. 13.
    Liu J, Guo Y, Zhang Y, Wang C, Liu M, Lv P, Lv S (2003) Relationship between infection of HPV-16, HSV-2, EBV, PCNA expression and cervical carcinoma. J Dalian Med Univ 25(2):85–87Google Scholar
  14. 14.
    Wu L, Xie D, Ren C, Sun Y, Zhong Y (2003) Expression of PCNA and ICAM-1 in cervical cnancer and significance. Med J Chin People’s Liber Army 28(7):165–169Google Scholar
  15. 15.
    Liu Y, Lin X, Liu H (2004) Study on apoptosis and the expression of P53 and PCNA in cervical cancer. Chin Clin Oncol 9(5):461–463Google Scholar
  16. 16.
    Sun H, Wang H, Qin T, Ruan Z, Ma J (2006) Expressions and significance of PCNA and MMP9 in cervix cancer tissue. J Fourth Mil Med Univ 27(22):2060–2062Google Scholar
  17. 17.
    Wang Y, Wang L, Zhao H, Wang Z, Li M (2006) Abnormal expression of hMSH2 and PCNA in cervical carcinoma. J Dalian Med Univ 28(5):373–375Google Scholar
  18. 18.
    Chen S, Zhang Y, Qu X (2007) The expression of Ki-67 and PCNA and their association with HPV infection in early-stage cervical carcinoma and CIN. Prog Obstetrics Gynecology 16(8):581–583Google Scholar
  19. 19.
    XIN H, GENG M, CHEN S, CHEN X, XU Z (2007) Evaluation of expressions and clinical significance of p16INK4a and PCNA in uterine cervix carcinoma and cervical intraepithelial neoplasia. Chin J Cancer Prev Treat 14(20):1563–1567Google Scholar
  20. 20.
    Cao Y, Geng M, Zheng J, Liu Y (2008) The expression and clinical significance of p16, p15 proteins and PCNA in uterine cervical carcinoma. Chin J Birth Health Hered 16(4):182–183Google Scholar
  21. 21.
    Bao C (2009) Expression and clinical significance of p53 and PCNA in cervical carcinoma. J Binzhou Med Univ 32(3):190–191Google Scholar
  22. 22.
    WANG S, JING J (2009) Expressions of PCNA and MMP-9 in cervix cancer tissue. J Zhengzhou Univ (Med Sci) 44(5):1040–1042Google Scholar
  23. 23.
    Zheng Q, Zheng Y, He Q (2009) The expression of fragile histidine triad (FHIT) and proliferating cell nuclear antigen (PCNA) in cervical intraepithelial neoplasia (CIN) and cervical cancer. Zhejiang Clin Med J 11(4):970–974Google Scholar
  24. 24.
    Wang H, Luo C, Lu Y, Liu M (2010) Study on expression and significance of MMP-9 and PCNA in cervical cancer by tissue microarray. Chin J Histochem Cytochem 19(5):457–462Google Scholar
  25. 25.
    Li Y (2014) Survivin, PTEN and PCNA expression in cervical cancer. Chin Pract Med 18:31–33Google Scholar
  26. 26.
    Wu Y (2015) Expression changes and significance of HMGB-1 and PCNA in cervical carcinoma. Shandong Med J 55(23):21–23Google Scholar
  27. 27.
    Duan G, Zhang X, Fei Z, Wu J, Fan Q, Liu X, Liang J, Wang X (2000) Relationship between cyclin A expression, cellular proliferation and pathological grade in human gliomas. J Fourth Mil Med Univ 21(9):1057–1059Google Scholar
  28. 28.
    Feng Q, Pan Q, Lei Y, Liao S, Zheng J (2003) Expression of p27Kip1, bcl-2 and PCNA proteins in gliomas. Pract J Cancer 18(5):476–480Google Scholar
  29. 29.
    Tan P, Li Z, Cai W, Lv J, Xie F, Weng Y (2003) Expression of nm23 and proliferating cell nuclear antigen (PCNA) in human brain gliomas and their significance. Chin J Cancer 22(10):1077–1080Google Scholar
  30. 30.
    Zhang Z, Liu C, Zhang X, Bao G, Han S (2004) Expression of nm23-H1 and PCNA in human glioma cells. J Xian Jiaotong Univ (Med Sci) 25(6):578–580Google Scholar
  31. 31.
    Wang D, Dai R, Liu N, Li Y, Cai J, Yan C (2007) Expressions and significance of PTTG and PCNA protein in glioma. Acta Univ Med Nanjing 27(9):1013–1015Google Scholar
  32. 32.
    Meng X, Liu Y, Wang M, Xie W (2008) Significance of PCNA and PTEN expressions in glioma tissue. J Fourth Mil Med Univ 29(7):660–662Google Scholar
  33. 33.
    Chen X, Peng C, Lv X (2009) The correlation between the expression of proliferation cell nuclear antigen and the recurrence of glioma. Pract J Cancer 24(5):455–461Google Scholar
  34. 34.
    Di H (2009) The expression of caveolin-1 and PCNA in gliomas. Heibei Univ 1(1):15–17Google Scholar
  35. 35.
    Zhang J, Chen H, Peng X, Weng R, Liu J, Ye H, Zhu Y, Zheng W et al (2009) Expression of IL-13Rα2 and PCNA in malignant glioma and its relationship with pathological characteristics and prognosis. Chin J Cancer Biother 16(5):516–519Google Scholar
  36. 36.
    Xu Z, Yuan X, Jiang P, Chen F, Gong R (2010) Expression and clinical significance of aurora A and PCNA in glioma. Med J Wuhan Univ 31(2):345–348Google Scholar
  37. 37.
    Zhao H (2010) Expression and significance of PTEN, E-cadherin and proliferating cell nuclear antigen in glioma. Chin J Med Guide 12(5):776–778Google Scholar
  38. 38.
    Wang F, Chen Z, Luo Y, Liu P, Chen L, Xia H (2012) Expression and correlation of Per2 and PCNA in glioma. Shandong Med J 52(26):7–9Google Scholar
  39. 39.
    Li J, Li H, Liu J, Feng B, Feng M, Lv B, Cheng S, Yang X (2015) The clinical implications of human telomerase reverse transcriptase expression in grade and prognosis of gliomas: a systematic review and meta-analysis. Mol NeurobiolGoogle Scholar
  40. 40.
    Celis JE, Madsen P, Nielsen S, Celis A (1986) Nuclear patterns of cyclin (PCNA) antigen distribution subdivide S-phase in cultured cells—some applications of PCNA antibodies. Leuk Res 10:237–349CrossRefPubMedGoogle Scholar
  41. 41.
    Leonardi E, Girlando S, Serio G, Mauri FA, Perrone G, Scampini S, Dalla Palma P, Barbareschi M (1992) PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables”. J Clin Pathol 45:416–419CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kelman Z (1997) PCNA: structure, functions and interactions. Oncogene 14:629–640CrossRefPubMedGoogle Scholar
  43. 43.
    Kuriyan J, O’Donnell M (1993) Sliding clamps of DNA polymerases. J Mol Biol 234:915–925CrossRefPubMedGoogle Scholar
  44. 44.
    Bowman GD, Goedken ER, Kazmirski SL, O’Donnell M, Kuriyan J (2005) DNA polymerase clamp loaders and DNA recognition. FEBS Lett 579:863–867CrossRefPubMedGoogle Scholar
  45. 45.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Qiongying Lv
    • 1
  • Juan Zhang
    • 1
  • Yuexiong Yi
    • 1
  • Yue Huang
    • 1
  • Yong Wang
    • 1
  • Yijun Wang
    • 1
  • Wei Zhang
    • 1
  1. 1.First Department of GynaecologyRenmin Hospital of Wuhan UniversityWuhanChina

Personalised recommendations