Expression and Clinical Significance of Placental Growth Factor in Gastric Cancer Tissue_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LUOJin-long ^1,2 ,  JIANGHuai-wu ¹

1. Department of Gastrointestinal Surgery, Sichuan Mianyang 404 Hospital, Mianyang 621000, Sichuan Province, China;
2. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Sichuan Province, China;

Corresponding?author：

JIANGHuai-wu, Email: jhuaiwu@163.com

Keywords：

Placental growth factor; Gastric cancer; Clinical significance

DOI：

10.7507/1007-9424.20150285

Video：

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Objective To investigate the relationship between placental growth factor (PlGF) and the gastric cancer. Methods The cancer tissues (cancer tissue group) and para-cancer tissues (para-cancer tissue group) of 88 patients with gastric cancer who underwent surgery in Sichuan Mianyang 404 Hospital from Mar. 2013 to Dec. 2014 were collected retrospectively, to determine the expressions of PlGF mRNA and its protein by polymerase chain reaction (PCR) and immunohistochemistry method. In addition, blood samples of 30 normal persons (normal person group) who got examina-tion in Sichuan Mianyang 404 Hospital in Sep. 2014 and 88 patients with gastric cancer (gastric cancer group) were collected to detect the concentration of serum PlGF, by using enzyme linked immunosorbent assay (ELISA). Comparison of the expressions of PlGF mRNA and its protein between cancer tissue group and para-cancer tissue group, concentration of PlGF between cancer tissue group and normal person group were performed, as well as the relationship between expressions of serum PlGF mRNA/PlGF in gastric cancer tissues and clinicopathological features of patients with gastric cancer, and relationship between concentration of PlGF in blood and clinicopathological features of patients with gastric cancer was explored by univariate analysis. Results The expression level of PlGF mRNA (0.569±0.166 vs. 0.037±0.020, t=-29.948, P=0.000) and positive-expression rate of PlGF[80.7% (71/88) vs. 5.7% (5/88), χ²=100.867, P=0.000] were significantly higher in cancer tissue group than those of para-cancer tissue group. And the concentration of PlGF in blood of patients in gastric cancer group was higher than that of normal person group[(57.247±9.800) ng/L vs. (10.351±1.715) ng/L, t=43.000, P=0.000]. The expressions of PlGF mRNA and its protein were both correlated with diameter of tumor, pT staging, pN staging, differentiation, and Borrmann type (P<0.050). The expression levels of PlGF mRNA and its protein in that patients with diameter of tumor greater than 4 cm, pT3-4 staging, pN3 staging, low differentiation, and Borrmann Ⅲ-Ⅳ staging were higher. While there were no significant correlation between expressions of PlGF mRNA/protein and age, gender, pM staging, and gastrointestinal type (P>0.050). Concentration of serum PlGF of gastric cancer patient wasn't significantly correlated with age, gender, diameter of tumor, pT staging, pN staging, pM staging, differentiation, Borrmann type, and gastrointestinal type (P>0.050). Conclusion The abnormal expression of PlGF at gastric cancer tissues may play an important role in pathogenesis of gastric cancer.

Citation： LUOJin-long, JIANGHuai-wu. Expression and Clinical Significance of Placental Growth Factor in Gastric Cancer Tissue. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(9): 1101-1106. doi: 10.7507/1007-9424.20150285 Copy

1.	?陳靜, 張德巍, 張春東, 等. 術前血清CEA、CA19-9水平檢測對胃癌術后復發轉移及預后的意義. 中國普外基礎與臨床雜志, 2015, 22(2):195-199.
2.	Rasmussen JG, Riis SE, Fr?bert O, et al. Activation of protease-activated receptor 2 induces VEGF independently of HIF-1. PLoS One, 2012, 7(9):e46087.
3.	石巖巖, 丁士剛. 胃癌病因及發病機制的研究進展. 中華臨床醫師雜志:電子版, 2013, 7(17):7941-7944.
4.	Adini A, Kornaga T, Firoozbakht F, et al. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res, 2002, 62(10):2749-2752.
5.	Chang LH, Pan SL, Lai CY, et al. Activated PAR-2 regulates panc-reatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis. Am J Pathol, 2013, 183(2):566-575.
6.	張示杰, 吳何興, 李琪, 等. 沙鼠肝泡球蚴組織中微血管密度、血管內皮生長因子的表達及意義. 中國普外基礎與臨床雜志, 2015, 22(2):134-138.
7.	Parr C, Watkins G, Boulton M, et al. Placenta growth factor is over-expressed and has prognostic value in human breast cancer. Eur J Cancer, 2005, 41(18):2819-2827.
8.	Matsumoto K, Suzuki K, Koike H, et al. Prognostic significance of plasma placental growth factor levels in renal cell cancer:an association with clinical characteristics and vascular endothelial growth factor levels. Anticancer Res, 2003, 23(6D):4953-4958.
9.	Woo IS, Park MJ, Byun JH, et al. Expression of placental growth factor gene in lung cancer. Tumor Biol, 2004, 25(1-2):1-6.
10.	Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma-2nd English edition. Gastric Cancer, 1998, 1(1):10-24.
11.	羅旭. PLGF、TGF β1和bFGF在膀胱移行細胞癌中的表達及臨床意義. 遵義:遵義醫學院, 2009:1-30.
12.	沈承瀾, 沈振斌, 陳偉東. 血管內皮生長因子、缺氧誘導因子-1α在胃癌中的表達及其對預后影響的研究. 中國全科醫學, 2010, 13(22):2460-2463.
13.	De Falco S. The discovery of placenta growth factor and its biolo-gical activity. Exp Mol Med, 2012, 44(1):1-9.
14.	Boyaud F, Inguimbert N. Soluble fms-like tyrosine kinase-1 antibody for diagnosis purposes (WO2010075475). Expert Opin Ther Pat, 2011, 21(6):971-975.
15.	Xu L, Cochran DM, Tong RT, et al. Placenta growth factor overex-pression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Res, 2006, 66(8):3971-3977.
16.	張力建, 陳晉峰, 陸愛萍, 等. 胎盤生長因子和色素上皮衍生因子在非小細胞肺癌中的表達及其與預后的關系. 中華醫學雜志, 2005, 85(47):3328-3331.
17.	Waldner MJ, Neurath MF. Colitis-associated cancer:the role of T cells in tumor development. Semin Immunopathol, 2009, 31(2):249-256.
18.	Fitzpatrick TE, Lash GE, Yanaihara A, et al. Inhibition of breast carcinoma and trophoblast cell invasiveness by vascular endothelial growth factor. Exp Cell Res, 2003, 283(2):247-255.
19.	Lenderink T, Heeschen C, Fichtlscherer S, et al. Elevated placental growth factor levels are associated with adverse outcomes at four-year follow-up in patients with acute coronary syndromes. J Am Coll Cardiol, 2006, 47(2):307-311.
20.	Takahashi A, Sasaki H, Kim SJ, et al. Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique. Biochem Biophys Res Commun, 1999, 257(3):855-859.
21.	Ho MC, Chen CN, Lee H, et al. Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma. Cancer Lett, 2007, 250(2):237-249.
22.	Hamady ZZ, Cameron IC, Wyatt J, et al. Resection margin in patients undergoing hepatectomy for colorectal liver metastasis:a critical appraisal of the 1 cm rule. Eur J Surg Oncol, 2006, 32(5):557-563.
23.	Kodama J, Seki N, Tokumo K, et al. Placenta growth factor is abundantly expressed in human cervical squamous cell carcinoma. Eur J Gynaecol Oncol, 1997, 18(6):508-510.
24.	Sands M, Howell K, Costello CM, et al. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung. Respir Res, 2011, 12:17.
25.	Yao J, Wu X, Zhuang G, et al. Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci U S A, 2011, 108(28):11590-11595.
26.	羅金龍, 姜淮蕪. 胎盤生長因子與腫瘤的研究進展. 中國普外基礎與臨床雜志, 2014, 21(8):1046-1050.

1. ?陳靜, 張德巍, 張春東, 等. 術前血清CEA、CA19-9水平檢測對胃癌術后復發轉移及預后的意義. 中國普外基礎與臨床雜志, 2015, 22(2):195-199.
2. Rasmussen JG, Riis SE, Fr?bert O, et al. Activation of protease-activated receptor 2 induces VEGF independently of HIF-1. PLoS One, 2012, 7(9):e46087.
3. 石巖巖, 丁士剛. 胃癌病因及發病機制的研究進展. 中華臨床醫師雜志:電子版, 2013, 7(17):7941-7944.
4. Adini A, Kornaga T, Firoozbakht F, et al. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res, 2002, 62(10):2749-2752.
5. Chang LH, Pan SL, Lai CY, et al. Activated PAR-2 regulates panc-reatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis. Am J Pathol, 2013, 183(2):566-575.
6. 張示杰, 吳何興, 李琪, 等. 沙鼠肝泡球蚴組織中微血管密度、血管內皮生長因子的表達及意義. 中國普外基礎與臨床雜志, 2015, 22(2):134-138.
7. Parr C, Watkins G, Boulton M, et al. Placenta growth factor is over-expressed and has prognostic value in human breast cancer. Eur J Cancer, 2005, 41(18):2819-2827.
8. Matsumoto K, Suzuki K, Koike H, et al. Prognostic significance of plasma placental growth factor levels in renal cell cancer:an association with clinical characteristics and vascular endothelial growth factor levels. Anticancer Res, 2003, 23(6D):4953-4958.
9. Woo IS, Park MJ, Byun JH, et al. Expression of placental growth factor gene in lung cancer. Tumor Biol, 2004, 25(1-2):1-6.
10. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma-2nd English edition. Gastric Cancer, 1998, 1(1):10-24.
11. 羅旭. PLGF、TGF β1和bFGF在膀胱移行細胞癌中的表達及臨床意義. 遵義:遵義醫學院, 2009:1-30.
12. 沈承瀾, 沈振斌, 陳偉東. 血管內皮生長因子、缺氧誘導因子-1α在胃癌中的表達及其對預后影響的研究. 中國全科醫學, 2010, 13(22):2460-2463.
13. De Falco S. The discovery of placenta growth factor and its biolo-gical activity. Exp Mol Med, 2012, 44(1):1-9.
14. Boyaud F, Inguimbert N. Soluble fms-like tyrosine kinase-1 antibody for diagnosis purposes (WO2010075475). Expert Opin Ther Pat, 2011, 21(6):971-975.
15. Xu L, Cochran DM, Tong RT, et al. Placenta growth factor overex-pression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Res, 2006, 66(8):3971-3977.
16. 張力建, 陳晉峰, 陸愛萍, 等. 胎盤生長因子和色素上皮衍生因子在非小細胞肺癌中的表達及其與預后的關系. 中華醫學雜志, 2005, 85(47):3328-3331.
17. Waldner MJ, Neurath MF. Colitis-associated cancer:the role of T cells in tumor development. Semin Immunopathol, 2009, 31(2):249-256.
18. Fitzpatrick TE, Lash GE, Yanaihara A, et al. Inhibition of breast carcinoma and trophoblast cell invasiveness by vascular endothelial growth factor. Exp Cell Res, 2003, 283(2):247-255.
19. Lenderink T, Heeschen C, Fichtlscherer S, et al. Elevated placental growth factor levels are associated with adverse outcomes at four-year follow-up in patients with acute coronary syndromes. J Am Coll Cardiol, 2006, 47(2):307-311.
20. Takahashi A, Sasaki H, Kim SJ, et al. Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique. Biochem Biophys Res Commun, 1999, 257(3):855-859.
21. Ho MC, Chen CN, Lee H, et al. Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma. Cancer Lett, 2007, 250(2):237-249.
22. Hamady ZZ, Cameron IC, Wyatt J, et al. Resection margin in patients undergoing hepatectomy for colorectal liver metastasis:a critical appraisal of the 1 cm rule. Eur J Surg Oncol, 2006, 32(5):557-563.
23. Kodama J, Seki N, Tokumo K, et al. Placenta growth factor is abundantly expressed in human cervical squamous cell carcinoma. Eur J Gynaecol Oncol, 1997, 18(6):508-510.
24. Sands M, Howell K, Costello CM, et al. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung. Respir Res, 2011, 12:17.
25. Yao J, Wu X, Zhuang G, et al. Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci U S A, 2011, 108(28):11590-11595.
26. 羅金龍, 姜淮蕪. 胎盤生長因子與腫瘤的研究進展. 中國普外基礎與臨床雜志, 2014, 21(8):1046-1050.

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Expression and Clinical Significance of Placental Growth Factor in Gastric Cancer Tissue

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