Skip to main content

Advertisement

Log in

Predictive significance of combined LAPTM4B and VEGF expression in patients with cervical cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

Lysosome-associated protein transmembrane 4ß-35 (LAPTM4B-35) is overexpressed in several solid malignancies. This study determines the expression level of LAPTM4B-35 in the cervical cancer during tumor development and progression. The present study investigated the clinicopathological significance of the coexpression of LAPTM4B-35 and VEGF in patients with cervical cancer. Immunohistochemistry was used to evaluate the expression of LAPTM4B-35 and VEGF in 62 cervical intraepithelial neoplasia (CIN) and 226 cervical carcinoma in comparison with 45 normal cervical specimens. The correlation of combined LAPTM4B-35 and VEGF with clinicopathologic characteristics was analyzed using a chi-squared test. Patient survival was determined using Kaplan–Meier method and log-rank test. A Cox regression analysis was performed to determine the prognostic significance of the factors. Combined LAPTM4B-35 and VEGF expression was significantly associated with FIGO stage (P = 0.014), tumor histologic grade (P = 0.033), lymph node metastasis (P = 0.045), and recurrence (P = 0.010). Kaplan–Meier survival analysis showed that patients with cervical cancer expressing both LAPTM4B-35 and VEGF exhibited both poor overall survival (OS) and disease-free survival (DFS) (P = 0.015 and P = 0.016, respectively). Cox analysis demonstrated that combined LAPTM4B-35 and VEGF expression was an independent factor for both OS and DFS (P = 0.015 and P = 0.016, respectively). Overexpression of LAPTM4B-35combined with positive VEGF expression may serve as a new biological marker to predict the prognosis of cervical carcinoma patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. de Sanjose S, Serrano B, Castellsague X, Brotons M, Munoz J, Bruni L, et al. Human papillomavirus (HPV) and related cancers in the global alliance for vaccines and immunization (GAVI) countries. A WHO/ICO HPV information centre report. Vaccine. 2012;30 Suppl 4:D1–D83. vi.

    PubMed  Google Scholar 

  2. Hwang SJ, Shroyer KR. Biomarkers of cervical dysplasia and carcinoma. J Oncol. 2012;2012:507286.

    Article  PubMed  Google Scholar 

  3. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382(9895):889–99.

    Article  PubMed  Google Scholar 

  4. Romanowski B. Long term protection against cervical infection with the human papillomavirus: review of currently available vaccines. Human vaccies. 2011;7(2):161–9.

    Article  Google Scholar 

  5. Shao GZ, Zhou RL, Zhang QY, Zhang Y, Liu JJ, Rui JA, et al. Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma. Oncogene. 2003;22(32):5060–9.

    Article  CAS  PubMed  Google Scholar 

  6. Yang H, Xiong F, Wei X, Yang Y, McNutt MA, Zhou R. Overexpression of LAPTM4B-35 promotes growth and metastasis of hepatocellular carcinoma in vitro and in vivo. Cancer Lett. 2010;294(2):236–44.

    Article  CAS  PubMed  Google Scholar 

  7. Zhou L, He XD, Yu JC, Zhou RL, Yang H, Qu Q, et al. Overexpression of LAPTM4B promotes growth of gallbladder carcinoma cells in vitro. Am J Surg. 2010;199(4):515–21.

    Article  CAS  PubMed  Google Scholar 

  8. Liu X, Xiong F, Wei X, Yang H, Zhou R. LAPTM4B-35, a novel tetratransmembrane protein and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells. Cancer Sci. 2009;100(12):2335–40.

    Article  CAS  PubMed  Google Scholar 

  9. Yang H, Xiong F, Qi R, Liu Z, Lin M, Rui J, et al. LAPTM4B-35 is a novel prognostic factor of hepatocellular carcinoma. J Surg Oncol. 2010;101(5):363–9.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang H, Tian B, Yu H, Yao H, Gao Z. LAPTM4B-35 protein as a potential therapeutic target in gastric cancer. Tumour Biol. 2014;35(12):12737–42.

    Article  CAS  PubMed  Google Scholar 

  11. Zhou L, He XD, Yu JC, Zhou RL, Shan Y, Rui JA. Overexpression of LAPTM4B-35 attenuates epirubucin-induced apoptosis of gallbladder carcinoma GBC-SD cells. Surgery. 2011;150(1):25–31.

    Article  PubMed  Google Scholar 

  12. Zhou L, He XD, Cui QC, Zhou WX, Qu Q, Zhou RL, et al. Expression of LAPTM4B-35: a novel marker of progression, invasiveness and poor prognosis of extrahepatic cholangiocarcinoma. Cancer Lett. 2008;264(2):209–17.

    Article  CAS  PubMed  Google Scholar 

  13. Kang Y, Yin M, Jiang W, Zhang H, Xia B, Xue Y, et al. Overexpression of LAPTM4B-35 is associated with poor prognosis in colorectal carcinoma. Am J Surg. 2012;204(5):677–83.

    Article  CAS  Google Scholar 

  14. Meng F, Luo C, Hu Y, Yin M, Lin M, Lou G, et al. Overexpression of LAPTM4B-35 in cervical carcinoma: a clinicopathologic study. Int J Gynecol Pathol. 2010;29(6):587–93.

    Article  CAS  PubMed  Google Scholar 

  15. Meng F, Chen X, Song H, Lou G. LAPTM4B down regulation inhibits the proliferation, invasion and angiogenesis of HeLa cells in vitro. Cell Physiol Biochem. 2015;37(3):890–900.

    Article  CAS  PubMed  Google Scholar 

  16. Folkman J, Kalluri R. Cancer without disease. Nature. 2004;427(6977):787.

    Article  CAS  PubMed  Google Scholar 

  17. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669–76.

    Article  CAS  PubMed  Google Scholar 

  18. Wang Y, Huang L, Wu S, Jia Y, Yang Y, Luo L, et al. Bioinformatics analyses of the role of vascular endothelial growth factor in patients with non-small cell lung cancer. PLoS One. 2015;10(9):e0139285.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Eswarappa SM, Fox PL. Antiangiogenic VEGF-Ax: a new participant in tumor angiogenesis. Cancer Res. 2015;75(14):2765–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Abdel-Rahman O. Targeting vascular endothelial growth factor (VEGF) pathway in iodine-refractory differentiated thyroid carcinoma (DTC): from bench to bedside. Crit Rev Oncol Hematol. 2015;94(1):45–54.

    Article  PubMed  Google Scholar 

  21. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: a Cancer J Clin. 2015;65(1):5–29.

    Google Scholar 

  22. Gadducci A, Lanfredini N, Sergiampietri C. Antiangiogenic agents in gynecological cancer: State of art and perspectives of clinical research. Crit Rev Oncol Hematol. 2015;96(1):113–28.

    Article  PubMed  Google Scholar 

  23. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer. 2002;2(10):727–39.

    Article  CAS  PubMed  Google Scholar 

  24. Rigiracciolo DC, Scarpelli A, Lappano R, Pisano A, Santolla MF, De Marco P, Cirillo F, Cappello AR, Dolce V, Belfiore A et al.: Copper activates HIF-1alpha/GPER/VEGF signalling in cancer cells. Oncotarget 2015

  25. Scartozzi M, Loretelli C, Galizia E, Mandolesi A, Pistelli M, Bittoni A, et al. Role of vascular endothelial growth factor (VEGF) and VEGF-R genotyping in guiding the metastatic process in pT4a resected gastric cancer patients. PLoS One. 2012;7(7):e38192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gremonprez F, Descamps B, Izmer A, Vanhove C, Vanhaecke F, Wever O, Ceelen W: Pretreatment with VEGF(R)-inhibitors reduces interstitial fluid pressure, increases intraperitoneal chemotherapy drug penetration, and impedes tumor growth in a mouse colorectal carcinomatosis model. Oncotarget 2015

  27. Zhang Y, Yu LK, Lu GJ, Xia N, Xie HY, Hu W, et al. Prognostic values of VEGF and endostatin with malignant pleural effusions in patients with lung cancer. Asian Pac J Cancer Prev. 2014;15(19):8435–40.

    Article  PubMed  Google Scholar 

  28. Koutras A, Kotoula V, Fountzilas G. Prognostic and predictive role of vascular endothelial growth factor polymorphisms in breast cancer. Pharmacogenomics. 2015;16(1):79–94.

    Article  CAS  PubMed  Google Scholar 

  29. Huang S, He P, Peng X, Li J, Xu D, Tang Y. Pristimerin inhibits prostate cancer bone metastasis by targeting PC-3 stem cell characteristics and VEGF-induced vasculogenesis of BM-EPCs. Cell Physiol Biochem. 2015;37(1):253–68.

    Article  CAS  PubMed  Google Scholar 

  30. Saijo Y, Furumoto H, Yoshida K, Nishimura M, Irahara M. Clinical significance of vascular endothelial growth factor expression and microvessel density in invasive cervical cancer. J Med Invest. 2015;62(3–4):154–60.

    Article  PubMed  Google Scholar 

  31. Dong J, Cheng M, Sun H. Function of inducible nitric oxide synthase in the regulation of cervical cancer cell proliferation and the expression of vascular endothelial growth factor. Mol Med Rep. 2014;9(2):583–9.

    CAS  PubMed  Google Scholar 

  32. Chen L, Wu YY, Liu P, Wang J, Wang G, Qin J, et al. Down-regulation of HPV18 E6, E7, or VEGF expression attenuates malignant biological behavior of human cervical cancer cells. Med Oncol. 2011;28 Suppl 1:S528–39.

    PubMed  Google Scholar 

  33. Huygens C, Lienart S, Dedobbeleer O, Stockis J, Gauthy E, Coulie PG, et al. Lysosomal-associated transmembrane protein 4B (LAPTM4B) decreases transforming growth factor beta1 (TGF-beta1) production in human regulatory T cells. J Biol Chem. 2015;290(33):20105–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Milkereit R, Persaud A, Vanoaica L, Guetg A, Verrey F, Rotin D. LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation. Nat Commun. 2015;6:7250.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Tang H, Tian H, Yue W, Li L, Li S, Gao C, et al. Overexpression of LAPTM4B is correlated with tumor angiogenesis and poor prognosis in non-small cell lung cancer. Med Oncol. 2014;31(6):974.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We express our thanks to Dr. H-T Song for the evaluation procedures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ge Lou.

Ethics declarations

Conflicts of interest

None

Grant support

This work was supported by grants of the National Natural Science Foundation of China (81201613), the Specialized Research Fund for the Doctoral Program of Higher Education (20122307120027), the Postdoctoral Foundation of Heilongjiang Province of China (LBH-Z11067), the scientific research project of Health Department of Heilongjiang Province (663), and the Haiyan Foundation of the Affiliated Tumor Hospital of Harbin Medical University/the Foundation of the Affiliated Tumor Hospital of Harbin Medical University (JJZ2011-04). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Additional information

Fanling Meng and Shu Tan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meng, F., Tan, S., Liu, T. et al. Predictive significance of combined LAPTM4B and VEGF expression in patients with cervical cancer. Tumor Biol. 37, 4849–4855 (2016). https://doi.org/10.1007/s13277-015-4319-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4319-9

Keywords

Navigation