Content of Stromal Cell Derived Factor-1αin Peripheral Blood of Patients with Gastric Adenocarcinoma and Its Clinical Significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WANGLu-bing ^1,2 , ZHUDeng-feng ² , HUANGLei ² , ZHANGChao-feng ² ,  JIANGBo-jian ¹

1. Department of General Surgery, Shanghai Third People's Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 201900, China;
2. Department of General Surgery, Xinhua Hospital Chongming Branch, Shanghai Jiao-tong University School of Medicine, Shanghai 202150, China;

Corresponding author：

JIANGBo-jian, Email: jiang_md@hotmail.com

Keywords：

Stomach; Neoplasm/cancer; Metastasis; Stromal cell derived factor-1α; Prognosis

DOI：

10.7507/1007-9424.20150347

Video：

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Objective To detect the content of stromal cell derived factor-1α(SDF-1α) in peripheral blood of patients with gastric adenocarcinoma (GC) and investigate its clinical significances. Methods The contents of SDF-1αin the peripheral blood of 90 patients with GC were detected by enzyme-linked immunosorbent assay. The correlation of SDF-1αcontent with the clinicopathologic parameters and prognosis after operation were analyzed. Results ①The content of SDF-1αin the patients with GC[(6950.8±1131.3) ng/L] was significantly higher than that in the normal healthy volunteers[(5023.7±1103.8) ng/l, P=0.036].②The content of SDF-1αin the GC patients with distant metastasis[(8251.6±1042.5) ng/L] was significantly higher than that without distant metastasis[(6785.3±1025.0) ng/L, P < 0.001]. The contents of SDF-1αin the peripheral blood of patients with distant metastasis either in the liver (P=0.002) or in the lung (P=0.030) were significantly higher than those without distant metastasis (liver or lung).③The TNM stage was later (P < 0.001), lymph node metastasis was broader (P=0.018), invasion of tumor was deeper (P < 0.001), vascular invasion (P < 0.001) and lymphatic vessel invasion were present (P < 0.001), the contents of SDF-1αwere higer. Logistic regression analysis revealed that the depth of tumor invasion (OR=14.999, 95% CI 3.568-74.456, P=0.027) and distant metastasis (OR=0.186, 95% CI 0.610-2.014, P=0.026) were correlated with the high SDF-1αcontent.④The survival time of the patients with higher content of SDF-1αwas significantly shorter than that of the lower content of SDF-1α(P < 0.001). Cox proportial hazard regression model analysis demonstrated that TNM stage (RR=2.497, 95% CI 1.987-10.238, P=0.009), vascular invasion (RR=7.501, 95% CI 2.086-16.942, P=0.002), and high content of SDF-1α(RR=18.302, 95% CI 6.895-30.538, P=0.001) in the peripheral blood were the independent risk factors for survival of the patients with GC. Conclusion High content of SDF-1αin peripheral blood might suggest the occurrence of lymph node metastasis, hepatic metastasis or lung metastasis and indicate the poorer prognosis of GC.

Citation： WANGLu-bing, ZHUDeng-feng, HUANGLei, ZHANGChao-feng, JIANGBo-jian. Content of Stromal Cell Derived Factor-1αin Peripheral Blood of Patients with Gastric Adenocarcinoma and Its Clinical Significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(11): 1327-1331. doi: 10.7507/1007-9424.20150347 Copy

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2.	Dubrovska A, Elliott J, Salamone RJ, et al. CXCR4 expression in prostate cancer progenitor cells. PLoS One, 2012, 7(2):e31226.
3.	Lee HJ, Lee K, Lee DG, et al. Chemokine (C-X-C motif) ligand 12 is associated with gallbladder carcinoma progression and is a novel independent poor prognostic factor. Clin Cancer Res, 2012, 18(12):3270-3280.
4.	Yao X, Zhou L, Han S, et al. High expression of CXCR4 and CXCR7 predicts poor survival in gallbladder cancer. J Int Med Res, 2011, 39(4):1253-1264.
5.	Zhang SS, Han ZP, Jing YY, et al. CD133(+) CXCR4(+) colon cancer cells exhibit metastatic potential and predict poor prognosis of patients. BMC Med, 2012, 10:85-99.
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8.	Lee HJ, Jo DY. The role of the CXCR4/CXCL12 axis and its clinical implications in gastric cancer. Histol Histopathol, 2012, 27(9):1155-1161.
9.	马天加, 张磊, 萧畔, 等. CIP2A在膀胱癌患者肿瘤组织及血清中的表达及其临床意义.中华医学杂志, 2014, 94(34):2681-2683.
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11.	Cavallaro S. CXCR4/CXCL12 in non-small-cell lung cancer metastasis to the brain. Int J Mol Sci, 2013, 14(1):1713-1727.
12.	Wani N, Nasser MW, Ahirwar DK, et al. C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment. Breast Cancer Res, 2014, 16(3):R54.
13.	Shin HN, Moon HH, Ku JL. Stromal cell-derived factor-1αand macrophage migration-inhibitory factor induce metastatic behavior in CXCR4-expressing colon cancer cells. Int J Mol Med, 2012, 30(6):1537-1543.
14.	Oh YS, Kim HY, Song IC, et al. Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α. Oncol Rep, 2012, 28(6):2239-2246.
15.	Satomura H, Sasaki K, Nakajima M, et al. Can expression of CXCL12 and CXCR4 be used to predict survival of gastric cancer patients? Anticancer Res, 2014, 34(8):4051-4057.
16.	Masuda T, Nakashima Y, Ando K, et al. Nuclear expression of chemokine receptor CXCR4 indicates poorer prognosis in gastric cancer. Anticancer Res, 2014, 34(11):6397-6403.
17.	Shibata W, Ariyama H, Westphalen CB, et al. Stromal cell-derived factor-1 overexpression induces gastric dysplasia through expansion of stromal myofibroblasts and epithelial progenitors. Gut, 2013, 62(2):192-200.
18.	Zhi Y, Chen J, Zhang S, et al. Down-regulation of CXCL12 by DNA hypermethylation and its involvement in gastric cancer metastatic progression. Dig Dis Sci, 2012, 57(3):650-659.
19.	Manu KA, Shanmugam MK, Rajendran P, et al. Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4. Mol Cancer, 2011, 10:107.
20.	Lee HJ, Song IC, Yun HJ, et al. CXC chemokines and chemokine receptors in gastric cancer:from basic findings towards therapeutic targeting. World J Gastroenterol, 2014, 20(7):1681-1693.
21.	Gawron AJ, Fought AJ, Lissowska J, et al. Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population. Scand J Gastroenterol, 2011, 46(3):333-340.
22.	周国才, 俞继卫, 陆瑞祺, 等. CXCR4和CD133 mRNA在胃腺癌原发灶中的表达及其临床意义.国际外科学杂志, 2012, 39(3):166-170.
23.	Wang X, Zhang H, He H, et al. Prognostic value of stromal cellderived factor 1 expression in patients with gastric cancer after surgical resection. Cancer Sci, 2014, 105(11):1447-1456.
24.	Koizumi K, Kato S, Sakurai H, et al. Therapeutics target of CXCR4 and its downstream in peritoneal carcinomatosis of gastric cancer. Front Biosci (Schol Ed), 2012, 4:269-276.

1. Sun X, Cheng G, Hao M, et al. CXCL12/CXCR4/CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev, 2010, 29(4):709-722.
2. Dubrovska A, Elliott J, Salamone RJ, et al. CXCR4 expression in prostate cancer progenitor cells. PLoS One, 2012, 7(2):e31226.
3. Lee HJ, Lee K, Lee DG, et al. Chemokine (C-X-C motif) ligand 12 is associated with gallbladder carcinoma progression and is a novel independent poor prognostic factor. Clin Cancer Res, 2012, 18(12):3270-3280.
4. Yao X, Zhou L, Han S, et al. High expression of CXCR4 and CXCR7 predicts poor survival in gallbladder cancer. J Int Med Res, 2011, 39(4):1253-1264.
5. Zhang SS, Han ZP, Jing YY, et al. CD133(+) CXCR4(+) colon cancer cells exhibit metastatic potential and predict poor prognosis of patients. BMC Med, 2012, 10:85-99.
6. 姜海广, 陆瑞祺, 吴巨钢, 等.基质细胞源性因子-1α/CXC趋化因子受体-4轴经PI3K/Akt通路对胃癌细胞CD133表达的调控作用.中华实验外科杂志, 2012, 29(3):378-380.
7. Zhao BC, Wang ZJ, Mao WZ, et al. CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma. World J Gastroenterol, 2011, 17(19):2389-2396.
8. Lee HJ, Jo DY. The role of the CXCR4/CXCL12 axis and its clinical implications in gastric cancer. Histol Histopathol, 2012, 27(9):1155-1161.
9. 马天加, 张磊, 萧畔, 等. CIP2A在膀胱癌患者肿瘤组织及血清中的表达及其临床意义.中华医学杂志, 2014, 94(34):2681-2683.
10. 陆瑞祺, 俞继卫, 姜波健. CXCL12(SDF-1)-CXCR4轴在胃癌中作用的研究进展.中国普通外科杂志, 2010, 19(4):430-433.
11. Cavallaro S. CXCR4/CXCL12 in non-small-cell lung cancer metastasis to the brain. Int J Mol Sci, 2013, 14(1):1713-1727.
12. Wani N, Nasser MW, Ahirwar DK, et al. C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment. Breast Cancer Res, 2014, 16(3):R54.
13. Shin HN, Moon HH, Ku JL. Stromal cell-derived factor-1αand macrophage migration-inhibitory factor induce metastatic behavior in CXCR4-expressing colon cancer cells. Int J Mol Med, 2012, 30(6):1537-1543.
14. Oh YS, Kim HY, Song IC, et al. Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α. Oncol Rep, 2012, 28(6):2239-2246.
15. Satomura H, Sasaki K, Nakajima M, et al. Can expression of CXCL12 and CXCR4 be used to predict survival of gastric cancer patients? Anticancer Res, 2014, 34(8):4051-4057.
16. Masuda T, Nakashima Y, Ando K, et al. Nuclear expression of chemokine receptor CXCR4 indicates poorer prognosis in gastric cancer. Anticancer Res, 2014, 34(11):6397-6403.
17. Shibata W, Ariyama H, Westphalen CB, et al. Stromal cell-derived factor-1 overexpression induces gastric dysplasia through expansion of stromal myofibroblasts and epithelial progenitors. Gut, 2013, 62(2):192-200.
18. Zhi Y, Chen J, Zhang S, et al. Down-regulation of CXCL12 by DNA hypermethylation and its involvement in gastric cancer metastatic progression. Dig Dis Sci, 2012, 57(3):650-659.
19. Manu KA, Shanmugam MK, Rajendran P, et al. Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4. Mol Cancer, 2011, 10:107.
20. Lee HJ, Song IC, Yun HJ, et al. CXC chemokines and chemokine receptors in gastric cancer:from basic findings towards therapeutic targeting. World J Gastroenterol, 2014, 20(7):1681-1693.
21. Gawron AJ, Fought AJ, Lissowska J, et al. Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population. Scand J Gastroenterol, 2011, 46(3):333-340.
22. 周国才, 俞继卫, 陆瑞祺, 等. CXCR4和CD133 mRNA在胃腺癌原发灶中的表达及其临床意义.国际外科学杂志, 2012, 39(3):166-170.
23. Wang X, Zhang H, He H, et al. Prognostic value of stromal cellderived factor 1 expression in patients with gastric cancer after surgical resection. Cancer Sci, 2014, 105(11):1447-1456.
24. Koizumi K, Kato S, Sakurai H, et al. Therapeutics target of CXCR4 and its downstream in peritoneal carcinomatosis of gastric cancer. Front Biosci (Schol Ed), 2012, 4:269-276.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Content of Stromal Cell Derived Factor-1αin Peripheral Blood of Patients with Gastric Adenocarcinoma and Its Clinical Significances

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