Skip to main content
SpringerLink
Log in

Prognostic value of peptidyl-prolyl cis–trans isomerase 1 (PIN1) in human malignant tumors

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Background

PIN1, a peptidyl-prolyl cis–trans isomerase, specifically can regulate phosphorylation of proteins on serine/threonine residues that precede proline and has critical roles in cell proliferation and transformation. Many studies have revealed that overexpression of PIN1 is involved in the malignant biological behavior of various cancers, but to date, no meta-analyses have evaluated PIN1 clinical and prognostic value in patients with malignant tumors.

Methods

We retrieved related articles from PubMed, Web of Science and Scopus databases up to April 20, 2019. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were used to estimate the correlation of PIN1 expression with clinicopathological characteristics and survival outcomes. The methodology was according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Collaboration guidelines.

Results

A total of 20 studies containing 2574 patients with various tumors were included in this analysis. Pooled results showed that PIN1 overexpression was significantly associated with the advanced clinical stages of cancer (OR = 1.37, 95% CI 1.06–1.78), positive lymph node metastasis (OR = 1.65, 95% CI 1.15–2.37) and poor prognosis (HR = 2.40, 95% CI 1.55–3.74), although no correlation with poor differentiation was found.

Conclusions

These results suggest that high expression of PIN1 can be considered as a risk factor for progression and invasion of malignant tumors and thus may serve as a promising therapeutic target and prognostic biomarker for human solid tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

PIN1:

Peptidyl-prolyl cis–trans isomerase 1

NSCLC:

Non-small cell lung cancer

PC:

Prostate cancer

ESCC:

Esophageal squamous cell carcinoma

EC:

Esophageal cancer

GC:

Gastric cancer

ECC:

Extrahepatic cholangiocarcinoma

SCCC:

Squamous cell carcinoma of cervix

CC:

Cervical cancer

PTC:

Papillary thyroid carcinoma

BC:

Breast cancer

BIDC:

Breast infiltrating duct carcinoma

CRC:

Colorectal cancer

GLC:

Glioma cancer

HNSCC:

Head and neck squamous cell carcinomas

SACC:

Salivary adenoid cystic carcinoma

MC:

Melanoma cancer

MCC:

Merkel cell carcinoma

HCC:

Hepatocellular carcinoma

OR:

Odd ratio

HR:

Hazard ratio

OS:

Overall survival

CI:

Confidence interval

DFS:

Disease-free survival

DSS:

Disease-specific survival

RFS:

Recurrence-free survival

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2018;68(6):394–424.

    Article  Google Scholar 

  2. Barton DP. Surgery for recurrent ovarian cancer. In: Devaja O, Papadopoulos A, editors. Ovarian cancer-from pathogenesis to treatment. Rijeka: IntechOpen; 2018. https://doi.org/10.5772/intechopen.71587.

    Chapter  Google Scholar 

  3. Kim H, Choi DH, Park W, Huh SJ, Nam SJ, Lee JE, et al. Prognostic factors for survivals from first relapse in breast cancer patients: analysis of deceased patients. Radiat Oncol J. 2013;31(4):222.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Asai N, Ohkuni Y, Kaneko N, Yamaguchi E, Kubo A. Relapsed small cell lung cancer: treatment options and latest developments. Ther Adv Med Oncol. 2014;6(2):69–82.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Neal R, Tharmanathan P, France B, Din N, Cotton S, Fallon-Ferguson J, et al. Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review. Br J Cancer. 2015;112(s1):S92.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos E. The challenge of drug resistance in cancer treatment: a current overview. Clin Exp Metastasis. 2018;35(4):309–18.

    Article  CAS  PubMed  Google Scholar 

  7. Chatterjee SK, Zetter BR. Cancer biomarkers: knowing the present and predicting the future. Future Oncol. 2005;1(1):37–50.

    Article  CAS  PubMed  Google Scholar 

  8. Chen Y, Wu Y, Yang H, Li X, Jie M, Hu C, et al. Prolyl isomerase Pin1: a promoter of cancer and a target for therapy. Cell Death Dis. 2018;9(9):1–17.

    Google Scholar 

  9. Ranganathan R, Lu KP, Hunter T, Noel JP. Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent. Cell. 1997;89(6):875–86.

    Article  CAS  PubMed  Google Scholar 

  10. Lu KP, Hanes SD, Hunter T. A human peptidyl–prolyl isomerase essential for regulation of mitosis. Nature. 1996;380(6574):544.

    Article  CAS  PubMed  Google Scholar 

  11. Ryo A, Nakamura M, Wulf G, Liou Y-C, Lu KP. Pin1 regulates turnover and subcellular localization of β-catenin by inhibiting its interaction with APC. Nat Cell Biol. 2001;3(9):793.

    Article  CAS  PubMed  Google Scholar 

  12. Zheng H, You H, Zhou XZ, Murray SA, Uchida T, Wulf G, et al. The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature. 2002;419(6909):849.

    Article  CAS  PubMed  Google Scholar 

  13. Wells NJ, Watanabe N, Tokusumi T, Jiang W, Verdecia MA, Hunter T. The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G (2)/M progression. J Cell Sci. 1999;112(19):3361–71.

    CAS  PubMed  Google Scholar 

  14. Miyashita H, Uchida T, Mori S, Echigo S, Motegi K. Expression status of Pin1 and cyclins in oral squamous cell carcinoma: Pin1 correlates with Cyclin D1 mRNA expression and clinical significance of cyclins. Oncol Rep. 2003;10(4):1045–8.

    CAS  PubMed  Google Scholar 

  15. Weiwad M, Küllertz G, Schutkowski M, Fischer G. Evidence that the substrate backbone conformation is critical to phosphorylation by p42 MAP kinase. FEBS Lett. 2000;478(1–2):39–42.

    Article  CAS  PubMed  Google Scholar 

  16. Wulf GM, Ryo A, Wulf GG, Lee SW, Niu T, Petkova V, et al. Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO J. 2001;20(13):3459–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kuramochi J, Arai T, Ikeda S, Kumagai J, Uetake H, Sugihara K. High Pin1 expression is associated with tumor progression in colorectal cancer. J Surg Oncol. 2006;94(2):155–60.

    Article  CAS  PubMed  Google Scholar 

  18. Zhu Z, Zhang H, Lang F, Liu G, Gao D, Li B, et al. Pin1 promotes prostate cancer cell proliferation and migration through activation of Wnt/beta-catenin signaling. Clin Transl Oncol. 2016;18(8):792–7. https://doi.org/10.1007/s12094-015-1431-7.

    Article  CAS  PubMed  Google Scholar 

  19. Jiang L, Chu H, Zheng H. Pin1 is related with clinical stage of papillary thyroid carcinoma. World J Surg Oncol. 2016;14(1):95.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang T, Liu Z, Shi F, Wang J. Pin1 modulates chemo-resistance by up-regulating FoxM1 and the involvements of Wnt/β-catenin signaling pathway in cervical cancer. Mol Cell Biochem. 2016;413(1–2):179–87.

    Article  CAS  PubMed  Google Scholar 

  21. Liu PH, Shah RB, Li Y, Arora A, Ung PM-U, Raman R, et al. An IRAK1–PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy. Nat Cell Biol. 2010;21(2):203.

    Article  CAS  Google Scholar 

  22. Tan X, Zhou F, Wan J, Hang J, Chen Z, Li B, et al. Pin1 expression contributes to lung cancer prognosis and carcinogenesis. Cancer Biol Ther. 2010;9(2):111–9.

    Article  CAS  PubMed  Google Scholar 

  23. Fukuchi M, Fukai Y, Kimura H, Sohda M, Miyazaki T, Nakajima M, et al. Prolyl isomerase Pin1 expression predicts prognosis in patients with esophageal squamous cell carcinoma and correlates with cyclinD1 expression. Int J Oncol. 2006;29(2):329–34.

    CAS  PubMed  Google Scholar 

  24. Fan G, Wang L, Xu J, Jiang P, Wang W, Huang Y, et al. Knockdown of the prolyl isomerase Pin1 inhibits Hep-2 cell growth, migration, and invasion by targeting the β-catenin signaling pathway. Biochem Cell Biol. 2018;96(6):734–41.

    Article  CAS  PubMed  Google Scholar 

  25. Karna SKL, Ahmad F, Lone BA, Pokharel YR. Knockdown of PTOV1 and PIN1 exhibit common phenotypic anti-cancer effects in MDA-MB-231 cells. PLoS ONE. 2019;14(5):e0211658.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ryo A, Uemura H, Ishiguro H, Saitoh T, Yamaguchi A, Perrem K, et al. Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer. Clin Cancer Res. 2005;11(20):7523–31.

    Article  CAS  PubMed  Google Scholar 

  27. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.

    Article  PubMed  Google Scholar 

  28. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8(5):336–41. https://doi.org/10.1016/j.ijsu.2010.02.007.

    Article  PubMed  Google Scholar 

  29. He J, Zhou F, Shao K, Hang J, Wang H, Rayburn E, et al. Overexpression of Pin1 in non-small cell lung cancer (NSCLC) and its correlation with lymph node metastases. Lung Cancer. 2007;56(1):51–8.

    Article  PubMed  Google Scholar 

  30. Fukuchi M, Fukai Y, Sohda M, Miyazaki T, Nakajima M, Inose T, et al. Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma. Oncol Rep. 2009;21(4):853–9.

    Article  CAS  PubMed  Google Scholar 

  31. Lin F-C, Lee Y-C, Goan Y-G, Tsai C-H, Yao Y-C, Cheng H-C, et al. Pin1 positively affects tumorigenesis of esophageal squamous cell carcinoma and correlates with poor survival of patients. J Biomed Sci. 2014;21(1):75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Jin H, Jiang J, Sun L, Zheng F, Wu C, Peng L, et al. The prolyl isomerase Pin1 is overexpressed in human esophageal cancer. Oncol Lett. 2011;2(6):1191–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shi M, Chen L, Ji J, Cai Q, Yu Y, Liu B, et al. Pin1 is overexpressed and correlates with poor prognosis in gastric cancer. Cell Biochem Biophys. 2015;71(2):857–64.

    Article  CAS  PubMed  Google Scholar 

  34. Jamiyandorj U, Bae JS, Noh SJ, Jachin S, Choi JE, Jang KY, et al. Expression of peptidyl-prolyl isomerase PIN1 and its role in the pathogenesis of extrahepatic cholangiocarcinoma. Oncol Lett. 2013;6(5):1421–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jawanjal P, Salhan S, Dhawan I, Tripathi R, Rath G. Peptidyl-prolyl isomerase Pin1-mediated abrogation of APC-β-catenin interaction in squamous cell carcinoma of cervix. Rom J Morphol Embryol. 2014;55(1):83–90.

    PubMed  Google Scholar 

  36. Hongyu L, Hongling S, Qian X, Dongrui D, Shixuan W, Yunping L, et al. Expression of Pin1 and Ki67 in cervical cancer and their significance. J Huazhong Univ Sci Technol [Medical Sciences]. 2006;26(1):120–2.

    Article  Google Scholar 

  37. Kim B-C, Han S-I, Lim S-C. Interpretation of Pin-1 and VEGF-C expression in breast infiltrating duct carcinoma. Oncol Rep. 2009;22(6):1381–90.

    CAS  PubMed  Google Scholar 

  38. Kim C-J, Cho Y-G, Park Y-G, Nam S-W, Kim S-Y, Lee S-H, et al. Pin1 overexpression in colorectal cancer and its correlation with aberrant β-catenin expression. World J Gastroenterol. 2005;11(32):5006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pyo J-S, Son BK, Oh IH. Cytoplasmic Pin1 expression is correlated with poor prognosis in colorectal cancer. Pathol Res Pract. 2018;214(11):1848–53.

    Article  CAS  PubMed  Google Scholar 

  40. Wiegand S, Dakic B, Rath AF, Makarova G, Sterz C, Meissner W, et al. The rotamase Pin1 is up-regulated, hypophosphorylated and required for cell cycle progression in head and neck squamous cell carcinomas. Oral Oncol. 2009;45(10):e140–e149.

    Article  CAS  PubMed  Google Scholar 

  41. Zhou C-X, Gao Y. Aberrant expression of β-catenin, Pin1 and cylin D1 in salivary adenoid cystic carcinoma: relation to tumor proliferation and metastasis. Oncol Rep. 2006;16(3):505–11.

    CAS  PubMed  Google Scholar 

  42. Chen X, Liu X, Deng B, Martinka M, Zhou Y, Lan X, et al. Cytoplasmic Pin1 expression is increased in human cutaneous melanoma and predicts poor prognosis. Sci Rep. 2018;8(1):16867.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Lill C, Schneider S, Pammer J, Loewe R, Gedlicka W, Houben R, et al. Significant correlation of peptidyl-prolyl isomerase overexpression in merkel cell carcinoma with overall survival of patients. Head Neck. 2011;33(9):1294–300.

    Article  PubMed  Google Scholar 

  44. Shinoda K, Kuboki S, Shimizu H, Ohtsuka M, Kato A, Yoshitomi H, et al. Pin1 facilitates NF-κB activation and promotes tumour progression in human hepatocellular carcinoma. Br J Cancer. 2015;113(9):1323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ayala G, Wang D, Wulf G, Frolov A, Li R, Sowadski J, et al. The prolyl isomerase Pin1 is a novel prognostic marker in human prostate cancer. Can Res. 2003;63(19):6244–51.

    CAS  Google Scholar 

  46. Yang Y, Niu C-S, Cheng C-D. Pin1-Nanog expression in human glioma is correlated with advanced tumor progression. Oncol Rep. 2013;30(2):560–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lill C, Schneider S, Seemann R, Kadletz L, Aumayr K, Ghanim B, et al. Correlation of β-catenin, but not PIN1 and cyclin D1, overexpression with disease-free and overall survival in patients with cancer of the parotid gland. Head Neck. 2015;37(1):30–6.

    Article  PubMed  Google Scholar 

  48. Girardini JE, Napoli M, Piazza S, Rustighi A, Marotta C, Radaelli E, et al. A Pin1/mutant p53 axis promotes aggressiveness in breast cancer. Cancer Cell. 2011;20(1):79–91.

    Article  CAS  PubMed  Google Scholar 

  49. Cheng C-W, Leong K-W, Tse E. Understanding the role of PIN1 in hepatocellular carcinoma. World J Gastroenterol. 2016;22(45):9921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lian X, Lin Y-M, Kozono S, Herbert MK, Li X, Yuan X, et al. Pin1 inhibition exerts potent activity against acute myeloid leukemia through blocking multiple cancer-driving pathways. J Hematol Oncol. 2018;11(1):73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Campaner E, Rustighi A, Zannini A, Cristiani A, Piazza S, Ciani Y, et al. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action. Nat Commun. 2017;8:15772.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by a grant from Hamadan University of Medical Sciences, Hamadan, Iran (9806054259).

Author information

Author notes

  1. S. G. Khoei and C. Mohammadi contributed equally to this manuscript.

Authors and Affiliations

  1. Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran

    S. G. Khoei, C. Mohammadi & S. Sameri

  2. Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Y. Mohammadi

  3. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Shahid Fahmideh Ave., 65178 38736, Hamadan, Iran

    R. Najafi

Authors
  1. S. G. Khoei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Sameri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Najafi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RN, SGK and CM were responsible for the conception and design of the review. SGK and CM conducted the database search and data collection. YM was responsible for the data analysis. SGK, CM and SS were involved in the interpretation of results and drafting the article. All the authors reviewed this draft, contributed and approved the final manuscript.

Corresponding author

Correspondence to R. Najafi.

Ethics declarations

Conflict of interest

SGK, CM, YM, SS and RN declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khoei, S.G., Mohammadi, C., Mohammadi, Y. et al. Prognostic value of peptidyl-prolyl cis–trans isomerase 1 (PIN1) in human malignant tumors. Clin Transl Oncol 22, 1067–1077 (2020). https://doi.org/10.1007/s12094-019-02233-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-019-02233-5

Keywords

Search

Navigation