Prognostic Significance of Serum Levels of Vascular Endothelial Growth Factor and Insulin-Like Growth Factor-Ⅰ in Advanced Gastric Cancer Patients Treated with FOLFOX Chemotherapy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 JINGuo-quan ¹ ,  LIMiao ²

1. Department of Oncological Surgery, The Fifth People's Hospital of Qinghai Province, Xining 810007, Qinghai Province, China;
2. Department of Medical Oncology, The Fifth People's Hospital of Qinghai Province, Xining 810007, Qinghai Province, China;

Corresponding?author：

LIMiao, Email: limiao1979@126.com

Keywords：

Vascular endothelial growth factor; Insulin-like growth factor-Ⅰ; Advanced gastric cancer; FOLFOX; Prognosis

DOI：

10.7507/1007-9424.20160372

Video：

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Objective To evaluate the prognostic significance of serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factors-Ⅰ (IGF-Ⅰ) in advanced gastric cancer patients who were treated with oxaliplatin/5-fluorouracil (FOLFOX). Methods Ninety-six advanced gastric cancer patients who were treated with FOLFOX in our hospital between March 2007 to August 2010 were enrolled in this study. All of the patients were treated with oxaliplatin (85 mg/m²) as a 2-hour infusion on day 1, and leucovorin (20 mg/m², about 10 min) on day 1 and day 2, followed by a 5-fluorouracil bolus (400 mg/m²) and 22 hours of continuous infusion of 600 mg/m². Treatment was repeated in 2-week intervals, and patients received 4 chemotherapy cycle in total. The levels of serum VEGF and IGF-Ⅰ were measured using enzyme-linked immunoassays. The relationship between serum levels of VEGF/IGF-Ⅰ and the clinicopathological characteristics of patients, the relationship between serum levels of VEGF/IGF-Ⅰ and prognosis of patients, were analyzed. Results The serum levels of VEGF and IGF-Ⅰ were (464.4±57.4) pg/mL and (33.5±7.3) ng/mL, respectively. The serum level of VEGF was related with surgical history, Lauren's classification, TNM staging before treatment, and pathological type (P < 0.05), and serum level of IGF-Ⅰ was related with TNM staging before treatment and number of transferred organs (P < 0.05). The serum levels of VEGF and IGF-Ⅰ in stable disease (SD) +progressive disease (PD) patiens were higher than those of complete response (CR) +partial response (PR) patients (P < 0.05). The results of Cox proportional hazard regression model showed that, effect of chemotherapy (HR=1.764, P=0.006), number of transferred organs (HR=1.662, P=0.015), serum level of VEGF (HR=1.834, P=0.012) and IGF-Ⅰ (HR=1.855, P=0.008), were all significantly related with time to progression (TTP); serum level of VEGF (HR=2.205, P=0.002) and IGF-Ⅰ (HR=1.931, P=0.004) were all significantly related with overall survival (OS). Conclusion Levels of serum VEGF and IGF-Ⅰ are independent prognostic factors in patients with advanced gastric cancer who were treated with FOLFOX chemotherapy.

Citation： JINGuo-quan, LIMiao. Prognostic Significance of Serum Levels of Vascular Endothelial Growth Factor and Insulin-Like Growth Factor-Ⅰ in Advanced Gastric Cancer Patients Treated with FOLFOX Chemotherapy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(12): 1470-1476. doi: 10.7507/1007-9424.20160372 Copy

1.	Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol, 2013, 107(3):230-236.
2.	鄒文斌, 李兆申.中國胃癌發病率及死亡率研究進展.中國實用內科雜志, 2014, 34(4):408-415.
3.	李振凱, 董茂盛.血清TGF-β1和IL-23在胃癌診斷中的臨床應用價值.中國普外基礎與臨床雜志, 2015, 22(11):1410-1415.
4.	陳博, 徐阿曼, 胡孔旺, 等.丙氨酰谷氨酰胺雙肽對存在營養風險胃癌患者臨床結局的影響.中國普外基礎與臨床雜志, 2016, 23(7):798-804.
5.	譚永剛, 耿東華, 蘇拓, 等.奧沙利鉑聯合氟尿嘧啶和亞葉酸鈣行新輔助化療治療進展期胃癌的臨床療效研究.中國全科醫學, 2012, 15(17):1937-1939.
6.	Miceli R, Tomasello G, Bregni G, et al. Adjuvant chemotherapy for gastric cancer:current evidence and future challenges. World J Gastroenterol, 2014, 20(16):4516-4525.
7.	Kim H, Yokoyama W, Davis PA. TRAMP prostate tumor growth is slowed by walnut diets through altered IGF-Ⅰ levels, energy pathways, and cholesterol metabolism. J Med Food, 2014, 17(12):1281-1286.
8.	Tee BC, Desai KG, Kennedy KS, et al. Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors. Am J Transl Res, 2016, 8(6):2693-2704.
9.	谷昌彥振りかける.新しい薬不良反応評価基準:NCI-CTC 2.0.日本の醫學を紹介し, 2001, 22(11):483-486.
10.	Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours:revised RECIST guideline (version 1.1). Eur J Cancer, 2009, 45(2):228-247.
11.	Thrumurthy SG, Chaudry MA, Hochhauser D, et al. The diagnosis and management of gastric cancer. BMJ, 2013, 347:f6367.
12.	Noh SH, Park SR, Yang HK, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC):5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol, 2014, 15(12):1389-1396.
13.	Wang J, Zhou Q, Li JY, et al. Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer. Chin J Cancer Res, 2014, 26(3):323-330.
14.	Gu J, Zou H, Zheng L, et al. GSTM1 null genotype is associated with increased risk of gastric cancer in both ever-smokers and non-smokers:a meta-analysis of case-control studies. Tumour Biol, 2014, 35(4):3439-3445.
15.	Pujol JL, Lavole A, Quoix E, et al. Randomized phase Ⅱ-Ⅲ study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer:results from the IFCT-0802 trial. Ann Oncol, 2015, 26(5):908-914.
16.	Pietrantonio F, De Braud F, Da Prat V, et al. A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res, 2013, 33(4):1257-1266.
17.	Villarejo-Campos P, Padilla-Valverde D, Martin RM, et al. Serum VEGF and VEGF-C values before surgery and after postoperative treatment in gastric cancer. Clin Transl Oncol, 2013, 15(4):265-270.
18.	Van Cutsem E, De Haas S, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer:a biomarker evaluation from the AVAGAST randomized phase Ⅲ trial. J Clin Oncol, 2012, 30(17):2119-2127.
19.	Yin L, Wang X, Luo C, et al. The value of expression of M2-PK and VEGF in patients with advanced gastric cancer. Cell Biochem Biophys, 2013, 67(3):1033-1039.
20.	Qian J, Zhou H, Chen J, et al. Genetic polymorphisms in IGF-Ⅰ and IGFBP-3 are associated with prostate cancer in the Chinese population. PLoS One, 2014, 9(2):e85609.
21.	González-Jiménez E, García PA, Aguilar MJ, et al. Breastfeeding and the prevention of breast cancer:a retrospective review of clinical histories. J Clin Nurs, 2014, 23(17-18):2397-2403.
22.	Seccareccia E, Brodt P. The role of the insulin-like growth factor-1 receptor in malignancy:an update. Growth Horm IGF Res, 2012, 22(6):193-199.
23.	Shitara K, Ito S, Misawa K, et al. Genetic polymorphism of IGF-Ⅰ predicts recurrence in patients with gastric cancer who have under-gone curative gastrectomy. Ann Oncol, 2012, 23(3):659-664.
24.	Chen C, Xu Y, Song Y. IGF-Ⅰ gene-modified muscle-derived stem cells are resistant to oxidative stress via enhanced activation of IGF-Ⅰ R/PI3K/AKT signaling and secretion of VEGF. Mol Cell Biochem, 2014, 386(1-2):167-175.
25.	Tang H, Liao Y, Chen G, et al. Estrogen upregulates the IGF-Ⅰ signaling pathway in lung cancer through estrogen receptor-β. Med Oncol, 2012, 29(4):2640-2648.

1. Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol, 2013, 107(3):230-236.
2. 鄒文斌, 李兆申.中國胃癌發病率及死亡率研究進展.中國實用內科雜志, 2014, 34(4):408-415.
3. 李振凱, 董茂盛.血清TGF-β1和IL-23在胃癌診斷中的臨床應用價值.中國普外基礎與臨床雜志, 2015, 22(11):1410-1415.
4. 陳博, 徐阿曼, 胡孔旺, 等.丙氨酰谷氨酰胺雙肽對存在營養風險胃癌患者臨床結局的影響.中國普外基礎與臨床雜志, 2016, 23(7):798-804.
5. 譚永剛, 耿東華, 蘇拓, 等.奧沙利鉑聯合氟尿嘧啶和亞葉酸鈣行新輔助化療治療進展期胃癌的臨床療效研究.中國全科醫學, 2012, 15(17):1937-1939.
6. Miceli R, Tomasello G, Bregni G, et al. Adjuvant chemotherapy for gastric cancer:current evidence and future challenges. World J Gastroenterol, 2014, 20(16):4516-4525.
7. Kim H, Yokoyama W, Davis PA. TRAMP prostate tumor growth is slowed by walnut diets through altered IGF-Ⅰ levels, energy pathways, and cholesterol metabolism. J Med Food, 2014, 17(12):1281-1286.
8. Tee BC, Desai KG, Kennedy KS, et al. Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors. Am J Transl Res, 2016, 8(6):2693-2704.
9. 谷昌彥振りかける.新しい薬不良反応評価基準:NCI-CTC 2.0.日本の醫學を紹介し, 2001, 22(11):483-486.
10. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours:revised RECIST guideline (version 1.1). Eur J Cancer, 2009, 45(2):228-247.
11. Thrumurthy SG, Chaudry MA, Hochhauser D, et al. The diagnosis and management of gastric cancer. BMJ, 2013, 347:f6367.
12. Noh SH, Park SR, Yang HK, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC):5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol, 2014, 15(12):1389-1396.
13. Wang J, Zhou Q, Li JY, et al. Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer. Chin J Cancer Res, 2014, 26(3):323-330.
14. Gu J, Zou H, Zheng L, et al. GSTM1 null genotype is associated with increased risk of gastric cancer in both ever-smokers and non-smokers:a meta-analysis of case-control studies. Tumour Biol, 2014, 35(4):3439-3445.
15. Pujol JL, Lavole A, Quoix E, et al. Randomized phase Ⅱ-Ⅲ study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer:results from the IFCT-0802 trial. Ann Oncol, 2015, 26(5):908-914.
16. Pietrantonio F, De Braud F, Da Prat V, et al. A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res, 2013, 33(4):1257-1266.
17. Villarejo-Campos P, Padilla-Valverde D, Martin RM, et al. Serum VEGF and VEGF-C values before surgery and after postoperative treatment in gastric cancer. Clin Transl Oncol, 2013, 15(4):265-270.
18. Van Cutsem E, De Haas S, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer:a biomarker evaluation from the AVAGAST randomized phase Ⅲ trial. J Clin Oncol, 2012, 30(17):2119-2127.
19. Yin L, Wang X, Luo C, et al. The value of expression of M2-PK and VEGF in patients with advanced gastric cancer. Cell Biochem Biophys, 2013, 67(3):1033-1039.
20. Qian J, Zhou H, Chen J, et al. Genetic polymorphisms in IGF-Ⅰ and IGFBP-3 are associated with prostate cancer in the Chinese population. PLoS One, 2014, 9(2):e85609.
21. González-Jiménez E, García PA, Aguilar MJ, et al. Breastfeeding and the prevention of breast cancer:a retrospective review of clinical histories. J Clin Nurs, 2014, 23(17-18):2397-2403.
22. Seccareccia E, Brodt P. The role of the insulin-like growth factor-1 receptor in malignancy:an update. Growth Horm IGF Res, 2012, 22(6):193-199.
23. Shitara K, Ito S, Misawa K, et al. Genetic polymorphism of IGF-Ⅰ predicts recurrence in patients with gastric cancer who have under-gone curative gastrectomy. Ann Oncol, 2012, 23(3):659-664.
24. Chen C, Xu Y, Song Y. IGF-Ⅰ gene-modified muscle-derived stem cells are resistant to oxidative stress via enhanced activation of IGF-Ⅰ R/PI3K/AKT signaling and secretion of VEGF. Mol Cell Biochem, 2014, 386(1-2):167-175.
25. Tang H, Liao Y, Chen G, et al. Estrogen upregulates the IGF-Ⅰ signaling pathway in lung cancer through estrogen receptor-β. Med Oncol, 2012, 29(4):2640-2648.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Prognostic Significance of Serum Levels of Vascular Endothelial Growth Factor and Insulin-Like Growth Factor-Ⅰ in Advanced Gastric Cancer Patients Treated with FOLFOX Chemotherapy

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