Serum IL-17F combined with VEGF as potential diagnostic biomarkers for oral squamous cell carcinoma
- 309 Downloads
Although interleukin (IL) 17A can promote angiogenesis in several tumors, there are limited clinical evidences on cancer about the correlation between serum vascular endothelial growth factor (VEGF) and IL-17F, which is the most homologous to IL-17A. In this study, serum concentration of IL-17F and VEGF from healthy (n = 28), leukoplakia (n = 15), and oral squamous cell carcinoma (OSCC) groups (n = 85) were assessed and showed that IL-17F level was remarkably downregulated from healthy group (394.3 pg/ml) to OSCC group (82.96 pg/ml). Conversely, the OSCC group had a highest level of VEGF (P < 0.05) in whole groups, and there was a negative correlation between IL-17F and VEGF in serum or in the peripheral blood mononuclear cells (PBMCs) at mRNA level. Moreover, the lowest ratio of IL-17F/VEGF was found in OSCC patients (P < 0.05) and lower ratio of IL-17F/VEGF correlated to higher tumor stage and lymph node metastasis. Furthermore, the serum level of IL-17F and the ratio of IL-17F/VEGF were positively associated with the numbers of CD3+ CD4+ T cells, which indicated that serum IL-17F could originate from PBMCs during the development of OSCC, and could be used for the diagnosis by effectively distinguishing OSCC patients from healthy individuals.
KeywordsIL-17F VEGF Oral squamous cell carcinoma CD4+ T cells Diagnosis
This work was supported by a grant from the National Natural Science Foundation of China (No. 81402238, 81072213 and 81271698), the Nanjing Medical Science & Research Project (No.YKK11039, YKK13145), Nanjing Medical Young Engineer (QRX113311), National Key Disciplines Constructional Project Funding (Since 2011), Jiangsu Provincial Clinical Medicine of Science and Technology project (Grant No BL2012017), Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012), and Center of Nanjing Clinical Medicine of tumor project (since 2014).
L.D., YH.N. and YY.H. designed experiments with valuable help from XF.H., EL.H., and QG.H. L.D. performed and analyzed data with valuable help from EL.H. and YJ.X. L.D. and DY.Z. wrote the manuscript. XF.H and B.L. collected surgical specimens; YY.H. and YH.N. oversaw the overall project.
Conflicts of interest
- 3.Genovese MC, Van den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, et al. LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum. 2010;62(4):929–39. doi: 10.1002/art.27334.CrossRefPubMedGoogle Scholar
- 5.Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont MC, Ranchin B, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10(7):778–85. doi: 10.1038/ni.1741.CrossRefPubMedGoogle Scholar
- 8.Melton AC, Melrose J, Alajoki L, Privat S, Cho H, Brown N, et al. Regulation of IL-17A production is distinct from IL-17F in a primary human cell co-culture model of T cell-mediated B cell activation. PLoS One. 2013;8(3):e58966. doi: 10.1371/journal.pone.0058966.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Starnes T, Robertson MJ, Sledge G, Kelich S, Nakshatri H, Broxmeyer HE, et al. Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol. 2001;167(8):4137–40.CrossRefPubMedGoogle Scholar
- 19.Benevides L, Cardoso CR, Tiezzi DG, Marana HR, Andrade JM, Silva JS. Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor. Eur J Immunol. 2013;43(6):1518–28. doi: 10.1002/eji.201242951.CrossRefPubMedGoogle Scholar