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Prognostic value of peptidyl-prolyl cistrans isomerase 1 (PIN1) in human malignant tumors

  • S. G. Khoei
  • C. Mohammadi
  • Y. Mohammadi
  • S. Sameri
  • R. NajafiEmail author
Research Article
  • 26 Downloads

Abstract

Background

PIN1, a peptidyl-prolyl cistrans 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.

Keywords

Peptidyl-prolyl cistrans isomerase 1 Meta‐analysis Prognostic marker Clinical characteristics 

Abbreviations

PIN1

Peptidyl-prolyl cistrans 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

Notes

Author 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.

Funding

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

Compliance with ethical standards

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.

References

  1. 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.CrossRefGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 7.
    Chatterjee SK, Zetter BR. Cancer biomarkers: knowing the present and predicting the future. Future Oncol. 2005;1(1):37–50.PubMedCrossRefGoogle Scholar
  8. 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. 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.PubMedCrossRefGoogle Scholar
  10. 10.
    Lu KP, Hanes SD, Hunter T. A human peptidyl–prolyl isomerase essential for regulation of mitosis. Nature. 1996;380(6574):544.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 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.CrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 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.PubMedPubMedCentralGoogle Scholar
  36. 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.CrossRefGoogle Scholar
  37. 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.PubMedPubMedCentralGoogle Scholar
  38. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedGoogle Scholar
  42. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 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.Google Scholar
  46. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 49.
    Cheng C-W, Leong K-W, Tse E. Understanding the role of PIN1 in hepatocellular carcinoma. World J Gastroenterol. 2016;22(45):9921.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 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.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Student Research CommitteeHamadan University of Medical SciencesHamadanIran
  2. 2.Modeling of Noncommunicable Diseases Research CenterHamadan University of Medical SciencesHamadanIran
  3. 3.Research Center for Molecular MedicineHamadan University of Medical SciencesHamadanIran

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