Abstract
Background
The purpose of this study is to evaluate serum levels of vascular endothelial growth factor (VEGF), pigment epithelium–derived factor (PEDF), tumor necrosis factor alpha (TNF-α), and progranulin in patients with gastric cancer (GC) and precancerous lesions (PCL) and to determine the usefulness of these markers as diagnostic biomarkers in these diseases.
Method
A total of 32 GC patients, 35 PCL patients, and 23 healthy controls participated in the study. The serum levels of VEGF, PEDF, TNF-α, and progranulin were measured by enzyme-linked immunosorbent assay (ELISA).
Results
The mean serum VEGF levels were 30.6 ± 12.98 pg/mL in GC, 18.2 ± 5.72 pg/mL in PCL, and 17.5 ± 5.59 pg/mL in controls. GC VEGF levels were significantly higher than both PCL and control groups (p < 0.001). The mean serum PEDF levels were 1516.1 ± 993.8 pg/mL in GC, 1039.1 ± 1002.3 pg/mL in PCL, and 767.5 ± 661.5 pg/mL in controls. The serum PEDF level in the GC group was significantly higher than that in both PCL and control groups (p = 0.004 and p = 0.038, respectively). The mean serum TNF-α levels were 46.7 ± 14.82 pg/mL in GC, 38.4 ± 11.89 pg/mL in PCL, and 33.8 ± 12.77 pg/mL in controls. There was a significant difference between GC and controls (p = 0.022) in TNF-α levels. The mean serum progranulin levels in GC were 2496.6 ± 737.8 pg/mL, 2332.0 ± 482.1 pg/mL in PCL, and 1288.7 ± 830.9 pg/mL in controls. Progranulin levels in both GC and PCL groups were significantly higher than that in the control group (p < 0.001 for both).
Conclusion
There were significant differences among patients with GC and PCL and healthy controls in terms of serum VEGF, PEDF, TNF-α, and progranulin levels.
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References
World Health Organization. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide. 2012, http://globocan.iarc. fr/Pages/fact_sheets_cancer. aspx (accessed June 20, 2016).
Yusefi AR, Bagheri Lankarani K, Bastani P, Radinmanesh M, Kavosi Z. Risk factors for gastric cancer: a systematic review. Asian Pac J Cancer Prev. 2018;19(3):591–603. https://doi.org/10.22034/APJCP.2018.19.3.591.
Arrington AK. Timing of chemotherapy and survival in patients with resectable gastric adenocarcinoma. World J Gastrointest Surg. 2013;5(12):321–8.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process–first American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res. 1992;52:6735–40.
Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–6. https://doi.org/10.1056/NEJM197111182852108.
Ding S, Lin S, Dong X, Yang X, Qu H, Huang S, et al. Potential prognostic value of circulating levels of vascular endothelial growth factor-A in patients with gastric cancer. In Vivo. 2005;19:793–5.
Vidal O, Metges JP, Elizalde I, Valentíni M, Volant A, Molina R, et al. High preoperative serum vascular endothelial growth factor levels predict poor clinical outcome after curative resection of gastric cancer. Br J Surg. 2009;96:1443–51.
Fernandez-Garcia NI, Volpert OV, Jimenez B. Pigment epithelium-derived factor as a multifunctional antitumor factor. J Mol Med (Berl). 2007;85(1):15–22. https://doi.org/10.1007/s00109-006-0111-z.
Zhang Y, Han J, Yang X, Shao C, Xu Z, Cheng R, et al. Pigment epithelium-derived factor inhibits angiogenesis and growth of gastric carcinoma by down-regulation of VEGF. Oncol Rep. 2011;26(3):681–6. https://doi.org/10.3892/or.2011.1318.
Forones NM, Mandowsky SV, Lourenço LG. Serum levels of interleukin-2 and tumor necrosis factor-alpha correlate to tumor progression in gastric cancer. Hepatogastroenterology. 2001;48(40):1199–201.
Demorrow S. Progranulin: a novel regulator of gastrointestinal cancer progression. Transl Gastrointest Cancer. 2013 Jul;2(3):145–51. https://doi.org/10.3978/j.issn.2224-4778.2013.02.02.
Linē A, Stengrēvics A, Slucka Z, Li G, Jankevics E, Rees RC. Serological identification and expression analysis of gastric cancer-associated genes. Br J Cancer. 2002;86(11):1824–30.
Yang D, Li R, Wang H, Wang J, Han L, Pan L, et al. Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways. Mol Med Rep. 2017;16(6):9685–91. https://doi.org/10.3892/mmr.2017.7796.
Wang XY, Wang LL, Zheng X, Meng LN, Lyu B, Jin HF. Expression of p-STAT3 and vascular endothelial growth factor in MNNG induced precancerous lesions and gastric tumors in rats. World J Gastrointest Oncol. 2016;8(3):305–13. https://doi.org/10.4251/wjgo.v8.i3.305.
Feng CW, Wang LD, Jiao LH, Liu B, Zheng S, Xie XJ. Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features. BMC Cancer. 2002;29(2):8.
Yakut M, Örmeci N, Erdal H, Keskin O, Karayel Z, Tutkak H, et al. The association between precancerous gastric lesions and serum pepsinogens, serum gastrin, vascular endothelial growth factor, serum interleukin-1 beta, serum toll-like receptor-4 levels and Helicobacter pylori cag A status. Clin Res Hepatol Gastroenterol. 2013;37(3):302–11. https://doi.org/10.1016/j.clinre.2012.09.013.
Senthilkumar C, Niranjali S, Jayanthi V, Ramesh T, Devaraj H. Molecular and histological evaluation of tumor necrosis factor-alpha expression in Helicobacter pylori-mediated gastric carcinogenesis. J Cancer Res Clin Oncol. 2011;137(4):577–83. https://doi.org/10.1007/s00432-010-0921-9.
Sánchez-Zauco N, Torres J, Gómez A, Camorlinga-Ponce M, Muñoz-Pérez L, Herrera-Goepfert R, et al. Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study. BMC Cancer. 2017;17(1):384. https://doi.org/10.1186/s12885-017-3310-9.
Erturk K, Tastekin D, Serilmez M, Bilgin E, Bozbey HU, Vatansever S. Clinical significance of serum interleukin-29, interleukin-32, and tumor necrosis factor alpha levels in patients with gastric cancer. Tumour Biol. 2016;37(1):405–12. https://doi.org/10.1007/s13277-015-3829-9.
Loei H, Tan HT, Lim TK, Lim KH, So JB, Yeoh KG, et al. Mining the gastric cancer secretome: identification of GRN as a potential diagnostic marker for early gastric cancer. J Proteome Res. 2012;11(3):1759–72. https://doi.org/10.1021/pr201014h.
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All procedures performed involving human participants were in accordance with the ethical standards of the institutional research committee (Keçiören Training and Research Hospital with reference number 01.2018/1601) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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Aksoy, E.K., Akpınar, M.Y., Doğan, Ö. et al. Clinical Significance of Serum Vascular Endothelial Growth Factor, Pigment Epithelium–Derived Factor, Tumor Necrosis Factor Alpha, and Progranulin Levels in Patients with Gastric Cancer and Gastric Precancerous Lesions. J Gastrointest Canc 50, 537–542 (2019). https://doi.org/10.1007/s12029-019-00251-8
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DOI: https://doi.org/10.1007/s12029-019-00251-8