Tumor Biology

, Volume 36, Issue 11, pp 8895–8902 | Cite as

KIF2A overexpression and its association with clinicopathologic characteristics and unfavorable prognosis in colorectal cancer

  • Xiangjun Fan
  • Xudong Wang
  • Huijun Zhu
  • Wei Wang
  • Shu Zhang
  • Zhiwei Wang
Research Article

Abstract

Kinesin superfamily protein 2A (KIF2A), an M‑type nonmotile microtubule depolymerase, has received attention for its role in carcinogenesis and prognostic value in several types of cancer. In this study, we evaluated the expression of KIF2A and its potential and robustness to predict clinical outcomes in colorectal cancer (CRC) patients. The messenger RNA (mRNA) expression of KIF2A was determined in 20 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. KIF2A immunohistochemistry was performed on tissue microarray (TMA), composed of 182 CRC and 179 matched adjacent nontumor tissues from surgery, 23 chronic colitis, 43 low-grade, and 18 high-grade intraepithelial neoplasias acquired through intestinal endoscopic biopsy. Univariate and multivariate Cox regression models were used to perform survival analyses. Both KIF2A mRNA and protein product exhibited CRC tissue-preferred expression, when compared with benign tissues. The high KIF2A expression was significantly correlated to TNM stage (P = 0.046) and tumor status (T) (P = 0.007). In univariate and multivariate analyses, high KIF2A expression showed a major prognostic value regarding 5-year survival. The influences of KIF2A expression on the survival were further proven by Kaplan–Meier survival analysis. This study demonstrated CRC tissue-preferred expression pattern of the KIF2A and suggested that high KIF2A expression might serve as an independent maker for poor prognosis in CRC patients.

Keywords

Kinesin family member 2A (KIF2A) Colorectal cancer (CRC) Biomarker Immunohistochemistry Prognosis 

Notes

Acknowledgments

This study was supported by the Technological Innovation and Demonstration of Social Undertakings Projects (HS2014049) of Nantong, Jiangsu, China, and the Translational Medicine Research (TDFzh2014001) from the Affiliated Hospital of Nantong University, Jiangsu, China.

Conflicts of interest

None.

References

  1. 1.
    Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22:191–7.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bosetti C, Bertuccio P, Malvezzi M, Levi F, Chatenoud L, Negri E, et al. Cancer mortality in europe, 2005–2009, and an overview of trends since 1980. Ann Oncol : official journal of the European Society for Medical Oncology / ESMO. 2013;24:2657–71.CrossRefGoogle Scholar
  3. 3.
    Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59:366–78.CrossRefPubMedGoogle Scholar
  4. 4.
    Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev : Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2009;18:1688–94.CrossRefGoogle Scholar
  5. 5.
    Sideris M, Papagrigoriadis S. Molecular biomarkers and classification models in the evaluation of the prognosis of colorectal cancer. Anticancer Res. 2014;34:2061–8.PubMedGoogle Scholar
  6. 6.
    Lee JK, Chan AT. Molecular prognostic and predictive markers in colorectal cancer: current status. Curr Colorectal Cancer Rep. 2011;7:136–44.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Markovic S, Antic J, Dimitrijevic I, Zogovic B, Bojic D, Svorcan P, et al. Microsatellite instability affecting the t17 repeats in intron 8 of hsp110, as well as five mononucleotide repeats in patients with colorectal carcinoma. Biomark Med. 2013;7:613–21.CrossRefPubMedGoogle Scholar
  8. 8.
    Domingo E, Ramamoorthy R, Oukrif D, Rosmarin D, Presz M, Wang H, et al. Use of multivariate analysis to suggest a new molecular classification of colorectal cancer. J Pathol. 2013;229:441–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Eklof V, Wikberg ML, Edin S, Dahlin AM, Jonsson BA, Oberg A, et al. The prognostic role of kras, braf, pik3ca and pten in colorectal cancer. Br J Cancer. 2013;108:2153–63.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lochhead P, Kuchiba A, Imamura Y, Liao X, Yamauchi M, Nishihara R, et al. Microsatellite instability and braf mutation testing in colorectal cancer prognostication. J Natl Cancer Inst. 2013;105:1151–6.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Li HY, Zhang Y, Cai JH, Bian HL. Microrna-451 inhibits growth of human colorectal carcinoma cells via downregulation of pi3k/akt pathway. Asian Pac J Cancer Prev : APJCP. 2013;14:3631–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Lou X, Qi X, Zhang Y, Long H, Yang J. Decreased expression of microrna-625 is associated with tumor metastasis and poor prognosis in patients with colorectal cancer. J Surg Oncol. 2013;108:230–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Yang IP, Tsai HL, Huang CW, Huang MY, Hou MF, Juo SH, et al. The functional significance of microrna-29c in patients with colorectal cancer: a potential circulating biomarker for predicting early relapse. PLoS One. 2013;8:e66842.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ishikawa K, Kamohara Y, Tanaka F, Haraguchi N, Mimori K, Inoue H, et al. Mitotic centromere-associated kinesin is a novel marker for prognosis and lymph node metastasis in colorectal cancer. Br J Cancer. 2008;98:1824–9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kline-Smith SL, Walczak CE. The microtubule-destabilizing kinesin xkcm1 regulates microtubule dynamic instability in cells. Mol Biol Cell. 2002;13:2718–31.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Manning AL, Ganem NJ, Bakhoum SF, Wagenbach M, Wordeman L, Compton DA. The kinesin-13 proteins kif2a, kif2b, and kif2c/mcak have distinct roles during mitosis in human cells. Mol Biol Cell. 2007;18:2970–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ganem NJ, Compton DA. The kini kinesin kif2a is required for bipolar spindle assembly through a functional relationship with mcak. J Cell Biol. 2004;166:473–8.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gaetz J, Kapoor TM. Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle poles. J Cell Biol. 2004;166:465–71.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wang CQ, Qu X, Zhang XY, Zhou CJ, Liu GX, Dong ZQ, et al. Overexpression of kif2a promotes the progression and metastasis of squamous cell carcinoma of the oral tongue. Oral Oncol. 2010;46:65–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Wang J, Ma S, Ma R, Qu X, Liu W, Lv C, et al. Kif2a silencing inhibits the proliferation and migration of breast cancer cells and correlates with unfavorable prognosis in breast cancer. BMC Cancer. 2014;14:461.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wang K, Lin C, Wang C, Shao Q, Gao W, Song B, et al. Silencing kif2a induces apoptosis in squamous cell carcinoma of the oral tongue through inhibition of the pi3k/akt signaling pathway. Molec Med Rep. 2014;9:273–8.Google Scholar
  22. 22.
    Schimizzi GV, Currie JD, Rogers SL. Expression levels of a kinesin-13 microtubule depolymerase modulates the effectiveness of anti-microtubule agents. PLoS One. 2010;5:e11381.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Han L, Jiang B, Wu H, Wang X, Tang X, Huang J, et al. High expression of cxcr2 is associated with tumorigenesis, progression, and prognosis of laryngeal squamous cell carcinoma. Med Oncol. 2012;29:2466–72.CrossRefPubMedGoogle Scholar
  24. 24.
    Sun R, Wang X, Zhu H, Mei H, Wang W, Zhang S, et al. Prognostic value of lamp3 and tp53 overexpression in benign and malignant gastrointestinal tissues. Oncotarget. 2014;5:12398–409.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Huang J, Zhang J, Li H, Lu Z, Shan W, Mercado-Uribe I, et al. Vcam1 expression correlated with tumorigenesis and poor prognosis in high grade serous ovarian cancer. Am J Transl Res. 2013;5:336–46.PubMedPubMedCentralGoogle Scholar
  26. 26.
    de Kok IM, Wong CS, Chia KS, Sim X, Tan CS, Kiemeney LA, et al. Gender differences in the trend of colorectal cancer incidence in singapore, 1968–2002. Int J Color Dis. 2008;23:461–7.CrossRefGoogle Scholar
  27. 27.
    Garcia-Alvarez A, Serra-Majem L, Ribas-Barba L, Castell C, Foz M, Uauy R, et al. Obesity and overweight trends in Catalonia, Spain (1992–2003): gender and socio-economic determinants. Public Health Nutr. 2007;10:1368–78.CrossRefPubMedGoogle Scholar
  28. 28.
    Austin H, Henley SJ, King J, Richardson LC, Eheman C. Changes in colorectal cancer incidence rates in young and older adults in the united states: what does it tell us about screening. Cancer Causes Control : CCC. 2014;25:191–201.CrossRefPubMedGoogle Scholar
  29. 29.
    Rath O, Kozielski F. Kinesins and cancer. Nat Rev Cancer. 2012;12:527–39.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhu C, Zhao J, Bibikova M, Leverson JD, Bossy-Wetzel E, Fan JB, et al. Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using rna interference. Mol Biol Cell. 2005;16:3187–99.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Honore S, Pasquier E, Braguer D. Understanding microtubule dynamics for improved cancer therapy. Cell Molec Life Sci : CMLS. 2005;62:3039–56.Google Scholar
  32. 32.
    McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, et al. Ras/raf/mek/erk and pi3k/pten/akt/mtor cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance. Oncotarget. 2012;3:1068–111.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chappell WH, Steelman LS, Long JM, Kempf RC, Abrams SL, Franklin RA, et al. Ras/raf/mek/erk and pi3k/pten/akt/mtor inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget. 2011;2:135–64.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Bader AG, Kang S, Zhao L, Vogt PK. Oncogenic pi3k deregulates transcription and translation. Nat Rev Cancer. 2005;5:921–9.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xiangjun Fan
    • 1
  • Xudong Wang
    • 2
  • Huijun Zhu
    • 3
  • Wei Wang
    • 3
  • Shu Zhang
    • 3
  • Zhiwei Wang
    • 1
  1. 1.Department of General SurgeryNantong University Affiliated HospitalNantongChina
  2. 2.Department of Laboratory MedicineNantong University Affiliated HospitalNantongChina
  3. 3.Department of PathologyNantong University Affiliated HospitalNantongChina

Personalised recommendations