成纤维细胞生长因子23在胃癌中的表达及作用研究
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摘要
目的:探讨成纤维细胞生长因子23(Fibroblast growth factor 23, FGF23)在胃癌中的表达,并研究其对胃癌细胞增殖和侵袭的作用。方法:收集2014年7月-2017年12月来我院手术治疗的胃癌患者,免疫组化检测FGF-23和Ki-67的表达;采用Transwell小室进行胃癌细胞侵袭实验;MTT实验检测胃癌细胞的增殖情况。结果:免疫组化的结果显示胃癌组FGF-23的平均光密度是477.5,对照组为46.65(t=10.53,P<0.0001),相关性分析的结果显示胃癌组织中FGF-23与Ki-67增殖指数具有正相关性(r=0.6489,P=0.0020);Transwell侵袭实验的结果显示低浓度的FGF-23具有一定的促进胃细胞侵袭的作用,高浓度的FGF-23能够显著的促进胃癌细胞侵袭,相对于对照组和低浓度组,侵袭的细胞数目分别上升了2.19倍和74.77%,结果差异明显(t=16.24,P<0.0001;t=9.811,P<0.0001);MTT实验的结果显示低浓度的FGF-23具有一定的促进胃细胞增殖的作用,高浓度的FGF-23能够显著的促进胃癌细胞增殖,相对于对照组和低浓度组,吸光度分别上升了1.70倍和37.37%倍,结果差异明显(t=13.81,P<0.0001;t=4.227,P=0.0018)。结论:我们的研究发现FGF-23在胃癌组织中高表达,其能促进胃癌细胞的增殖和侵袭,我们的研究为胃癌的诊断和精准治疗提供了一个新的靶点。
Objective: To investigate the expression of Fibroblast growth factor(FGF23) in gastric cancer and to study the effect of Fibroblast on the proliferation and invasion of gastric cancer cells. Methods: We collected gastric cancer patients who underwent surgical treatment in our hospital from July 2014 to December 2017. Immunohistochemistry was used to detect the expression of FGF-23 and Ki-67. Transwell was used to detect gastric cancer cell invasion and MTT assay was used to detect the proliferation of gastric cancer cells. Results: Immunohistochemistry showed that the average optical density of FGF-23 in gastric cancer group was 477.5, and that in control group was 46.65(t=10.53, P<0.0001). Correlation analysis showed that there was a positive correlation between FGF-23 and Ki-67 proliferation index in gastric cancer(r=0.6489, P=0.0020). The Transwell invasion experiment showed that low concentration of FGF-23 had a certain effect on the invasion of gastric cells, and the high concentration of FGF-23 could significantly promote the invasion of gastric cancer cells. Compared with the control group and low concentration group, the number of invasive cells increased by 2.19 times and 74.77%, respectively(t=16.24, P<0.0001; t=9.811, P<0.0001); The results of the MTT experiment showed that low concentration of FGF-23 had a certain effect on promoting the proliferation of gastric cells. The high concentration of FGF-23 could significantly promote the proliferation of gastric cancer cells. Compared with the control group and the low concentration group, the absorbency increased by 1.70 times and 37.37% times respectively. The results were significantly different(t=13.81, P<0.0001; t=4.227, P=0.0018).Conclusion: Our study found that FGF-23 is highly expressed in gastric cancer tissue, which can promote the proliferation and invasion of gastric cancer cells. Our study provides a new target for the diagnosis and accurate treatment of gastric cancer.
Objective: To investigate the expression of Fibroblast growth factor(FGF23) in gastric cancer and to study the effect of Fibroblast on the proliferation and invasion of gastric cancer cells. Methods: We collected gastric cancer patients who underwent surgical treatment in our hospital from July 2014 to December 2017. Immunohistochemistry was used to detect the expression of FGF-23 and Ki-67. Transwell was used to detect gastric cancer cell invasion and MTT assay was used to detect the proliferation of gastric cancer cells. Results: Immunohistochemistry showed that the average optical density of FGF-23 in gastric cancer group was 477.5, and that in control group was 46.65(t=10.53, P<0.0001). Correlation analysis showed that there was a positive correlation between FGF-23 and Ki-67 proliferation index in gastric cancer(r=0.6489, P=0.0020). The Transwell invasion experiment showed that low concentration of FGF-23 had a certain effect on the invasion of gastric cells, and the high concentration of FGF-23 could significantly promote the invasion of gastric cancer cells. Compared with the control group and low concentration group, the number of invasive cells increased by 2.19 times and 74.77%, respectively(t=16.24, P<0.0001; t=9.811, P<0.0001); The results of the MTT experiment showed that low concentration of FGF-23 had a certain effect on promoting the proliferation of gastric cells. The high concentration of FGF-23 could significantly promote the proliferation of gastric cancer cells. Compared with the control group and the low concentration group, the absorbency increased by 1.70 times and 37.37% times respectively. The results were significantly different(t=13.81, P<0.0001; t=4.227, P=0.0018).Conclusion: Our study found that FGF-23 is highly expressed in gastric cancer tissue, which can promote the proliferation and invasion of gastric cancer cells. Our study provides a new target for the diagnosis and accurate treatment of gastric cancer.
引文
[1] Petroianu A. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer[J]. Cancer, 2015, 72(1):37-41
[2] Van C E, De H S, Kang Y K, 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]. Journal of Clinical Oncology, 2012, 30(17):2119-2127
[3] David V, Martin A, Isakova T, et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production[J]. Kidney International, 2016, 89(1):135-146
[4] Singh S, Grabner A, Yanucil C, et al. Fibroblast growth factor 23 directly targets hepatocytes to promote inflammation in chronic kidney disease[J]. Kidney International, 2016, 90(5):985-996
[5] Qin Z, Xi L, Song M, et al. Fibroblast growth factor 23 as a predictor of cardiovascular and all-cause mortality in prospective studies[J].Atherosclerosis, 2017, 261:1-11
[6] Feng S, Wang J, Zhang Y, et al. FGF23 promotes prostate cancer progression[J]. Clinical Cancer Research An Official Journal of the American Association for Cancer Research, 2015, 6(19):17291-17301
[7] Zhang J Z, Liu C M, Peng H P, et al. Association of genetic variations in IL-6/IL-6R pathway genes with gastric cancer risk in a Chinese population[J]. Gene, 2017, 623:1-4
[8] Zhang H, Deng T, Liu R, et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis[J]. Nature Communications, 2017, 8:15016
[9] Al-U'Datt D G, Al-Husein B A, Qasaimeh G R. A mini-review of c-Met as a potential therapeutic target in melanoma[J]. Biomedicine&Pharmacotherapy, 2017, 88:194-202
[10] Hughes P E, Caenepeel S, Wu L C. Targeted Therapy and Checkpoint Immunotherapy Combinations for the Treatment of Cancer[J]. Trends in Immunology, 2016, 37(7):462-476
[11] Katoh M, Nakagama H. FGF Receptors:Cancer Biology and Therapeutics[J]. Medicinal Research Reviews, 2014, 34(2):280-300
[12] Sawey E T, Chanrion M, Cai C, et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening[J]. Cancer Cell, 2011, 19(3):347-358
[13] Knights V, Cook S J. De-regulated FGF receptors as therapeutic targets in cancer[J]. Pharmacology&Therapeutics, 2010, 125(1):105-117
[14] Khurana A, Liu P, Mellone P, et al. HSulf-1 Modulates FGF-2 and Hypoxia Mediated Migration and Invasion of Breast Cancer Cells[J].Cancer Research, 2011, 71(6):2152-2161
[15] Leaf D E, Pereira R C, Bazari H, et al. Oncogenic osteomalacia due to FGF23-expressing colon adenocarcinoma[J]. Journal of Clinical Endocrinology&Metabolism, 2013, 98(3):887-891
[16] Yamada S, Giachelli C M. Vascular calcification in CKD-MBD:Roles for phosphate, FGF23, and Klotho[J]. Bone, 2017, 100:87-93
[17] Kuro-O M, Moe O W. FGF23-αKlotho as a paradigm for a kidneybone network[J]. Bone, 2016, 100:4-18
[18] Schlitt A, Sester U, Sester M, et al. Letter to the Editor regarding Dounousi E et al. Intact FGF23 andα-Klotho during acute inflammation/sepsis in CKD patients[J]. European Journal of Clinical Investigation, 2017, 47(6):468-469
[19] Kim H J, Kim K H, Lee J, et al. Single nucleotide polymorphisms in fibroblast growth factor 23 gene, FGF23, are associated with prostate cancer risk[J]. Bju International, 2013, 114(2):303-310
[20] Lee E K, Martinez M C, Blakely K, et al. FGF23:mediator of poor prognosis in a sizeable subgroup of patients with castration-resistant prostate cancer presenting with severe hypophosphatemia?[J]. Medical Hypotheses, 2014, 83(4):482-487
[21] Vlot M C, Bijnsdorp I, Den M H, et al. Plasma FGF23 is not elevated in prostate cancer[J]. Clinica Chimica Acta, 2017, 478:129-131
[22] Lee E K, Martinez M C, Blakely K, et al. FGF23, prostate cancer[J].Medical Hypotheses, 2014, 83(4):482-487
[2] Van C E, De H S, Kang Y K, 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]. Journal of Clinical Oncology, 2012, 30(17):2119-2127
[3] David V, Martin A, Isakova T, et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production[J]. Kidney International, 2016, 89(1):135-146
[4] Singh S, Grabner A, Yanucil C, et al. Fibroblast growth factor 23 directly targets hepatocytes to promote inflammation in chronic kidney disease[J]. Kidney International, 2016, 90(5):985-996
[5] Qin Z, Xi L, Song M, et al. Fibroblast growth factor 23 as a predictor of cardiovascular and all-cause mortality in prospective studies[J].Atherosclerosis, 2017, 261:1-11
[6] Feng S, Wang J, Zhang Y, et al. FGF23 promotes prostate cancer progression[J]. Clinical Cancer Research An Official Journal of the American Association for Cancer Research, 2015, 6(19):17291-17301
[7] Zhang J Z, Liu C M, Peng H P, et al. Association of genetic variations in IL-6/IL-6R pathway genes with gastric cancer risk in a Chinese population[J]. Gene, 2017, 623:1-4
[8] Zhang H, Deng T, Liu R, et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis[J]. Nature Communications, 2017, 8:15016
[9] Al-U'Datt D G, Al-Husein B A, Qasaimeh G R. A mini-review of c-Met as a potential therapeutic target in melanoma[J]. Biomedicine&Pharmacotherapy, 2017, 88:194-202
[10] Hughes P E, Caenepeel S, Wu L C. Targeted Therapy and Checkpoint Immunotherapy Combinations for the Treatment of Cancer[J]. Trends in Immunology, 2016, 37(7):462-476
[11] Katoh M, Nakagama H. FGF Receptors:Cancer Biology and Therapeutics[J]. Medicinal Research Reviews, 2014, 34(2):280-300
[12] Sawey E T, Chanrion M, Cai C, et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening[J]. Cancer Cell, 2011, 19(3):347-358
[13] Knights V, Cook S J. De-regulated FGF receptors as therapeutic targets in cancer[J]. Pharmacology&Therapeutics, 2010, 125(1):105-117
[14] Khurana A, Liu P, Mellone P, et al. HSulf-1 Modulates FGF-2 and Hypoxia Mediated Migration and Invasion of Breast Cancer Cells[J].Cancer Research, 2011, 71(6):2152-2161
[15] Leaf D E, Pereira R C, Bazari H, et al. Oncogenic osteomalacia due to FGF23-expressing colon adenocarcinoma[J]. Journal of Clinical Endocrinology&Metabolism, 2013, 98(3):887-891
[16] Yamada S, Giachelli C M. Vascular calcification in CKD-MBD:Roles for phosphate, FGF23, and Klotho[J]. Bone, 2017, 100:87-93
[17] Kuro-O M, Moe O W. FGF23-αKlotho as a paradigm for a kidneybone network[J]. Bone, 2016, 100:4-18
[18] Schlitt A, Sester U, Sester M, et al. Letter to the Editor regarding Dounousi E et al. Intact FGF23 andα-Klotho during acute inflammation/sepsis in CKD patients[J]. European Journal of Clinical Investigation, 2017, 47(6):468-469
[19] Kim H J, Kim K H, Lee J, et al. Single nucleotide polymorphisms in fibroblast growth factor 23 gene, FGF23, are associated with prostate cancer risk[J]. Bju International, 2013, 114(2):303-310
[20] Lee E K, Martinez M C, Blakely K, et al. FGF23:mediator of poor prognosis in a sizeable subgroup of patients with castration-resistant prostate cancer presenting with severe hypophosphatemia?[J]. Medical Hypotheses, 2014, 83(4):482-487
[21] Vlot M C, Bijnsdorp I, Den M H, et al. Plasma FGF23 is not elevated in prostate cancer[J]. Clinica Chimica Acta, 2017, 478:129-131
[22] Lee E K, Martinez M C, Blakely K, et al. FGF23, prostate cancer[J].Medical Hypotheses, 2014, 83(4):482-487