LAPTM4B-35和MMP-9在胃癌中表达及临床意义
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摘要
目的:本研究分析溶酶体相关4次跨膜蛋白B(lysosome-associated transmembrane protein 4β,LAPTM4B)-35和基质金属蛋白酶(matrix metalloproteinase,MMP)-9在胃癌中的表达及其与临床病理因素和预后的关系。方法:采用q RT-PCR法检测胃癌细胞株及正常胃黏膜细胞株中LAPTM4B-35和MMP-9 m RNA的表达,免疫组织化学分析胃癌石蜡标本LAPTM4B-35和MMP-9蛋白的表达,运用相关手段分析蛋白表达与临床相关性,Log-rank单因素分析和Cox多因素分析对预后进行研究。结果:LAPTM4B-35和MMP-9 m RNA在HGC-27、SGC7901和MGC803胃癌细胞株相对表达量明显高于GES-1胃黏膜细胞株;免疫组织化学结果显示LAPTM4B-35和MMP-9均在细胞质中表达,LAPTM4B-35阳性表达率为50.7%,MMP-9阳性表达率为36.8%;LAPTM4B-35的表达与MMP-9的表达呈正相关;相关分析显示Lauren's分型和肿瘤浸润T分期与LAPTM4B-35表达相关,肿瘤大小和淋巴结转移N分期与MMP-9表达密切相关,预后生存Cox多因素分析结果显示分化程度、淋巴结转移N分期、LAPTM4B-35表达与MMP-9表达是胃癌患者独立预后因素。结论:LAPTM4B-35和MMP-9在胃癌的侵袭和迁移中起着重要作用,其表达为胃癌预后独立因素,可作为胃癌预后指标。
Objective: To investigate the protein expression level of lysosome-associated transmembrane protein 4β-35(LAPTM4 B-35)and matrix metalloproteinase-9(MMP-9) in gastric cancer(GC) and to determine the relationship of LAPTM 4 B-35 or MMP-9 expression with clinicopathological characteristics and prognosis of patients with GC.Methods: The messenger RNA(m RNA) expression level of LAPTM4 B-35 and MMP-9 was detected by real-time quantitative polymerase chain reaction,while the protein expression level of LAPTM 4 B-35 and MMP-9 in GC tissues was analyzed by immunohistochemistry in formalin-fixed samples from 152 patients with GC,and data analysis was performed using statistical methods.Results: The m RNA expression level of both LAPTM4 B-35 and MMP-9 in HGC-27,SGC 7901,and MGC803 GC cell lines was higher than that in the GES-1 normal gastric mucosa cell line.LAPTM 4 B-35 and MMP-9 proteins mainly localized in the cytoplasm of GC cells.The positive LAPTM4 B-35 expression ratio in GC tissues was 50.7%,while the MMP-9 positive ratio was 36.8%.LAPTM4 B-35 and MMP-9 were positively related to gastric cancer.Lauren's classification and T stage were identified as the relative factors of LAPTM4 B-35 expression,while tumor size and N stage were identified as the relative factors of MMP-9 expression in GC tissues.Cox analysis indicated that the degree of differentiation,N stage,LAPTM 4 B-35 expression,and MMP-9 expression were independent prognostic indicators for patients with GC.Conclusion: LAPTM4 B-35 and MMP-9 play important roles in the aggressiveness of GC,and LAPTM4 B-35 and MMP-9 may be promising indicators for the prognosis of patients with GC.
Objective: To investigate the protein expression level of lysosome-associated transmembrane protein 4β-35(LAPTM4 B-35)and matrix metalloproteinase-9(MMP-9) in gastric cancer(GC) and to determine the relationship of LAPTM 4 B-35 or MMP-9 expression with clinicopathological characteristics and prognosis of patients with GC.Methods: The messenger RNA(m RNA) expression level of LAPTM4 B-35 and MMP-9 was detected by real-time quantitative polymerase chain reaction,while the protein expression level of LAPTM 4 B-35 and MMP-9 in GC tissues was analyzed by immunohistochemistry in formalin-fixed samples from 152 patients with GC,and data analysis was performed using statistical methods.Results: The m RNA expression level of both LAPTM4 B-35 and MMP-9 in HGC-27,SGC 7901,and MGC803 GC cell lines was higher than that in the GES-1 normal gastric mucosa cell line.LAPTM 4 B-35 and MMP-9 proteins mainly localized in the cytoplasm of GC cells.The positive LAPTM4 B-35 expression ratio in GC tissues was 50.7%,while the MMP-9 positive ratio was 36.8%.LAPTM4 B-35 and MMP-9 were positively related to gastric cancer.Lauren's classification and T stage were identified as the relative factors of LAPTM4 B-35 expression,while tumor size and N stage were identified as the relative factors of MMP-9 expression in GC tissues.Cox analysis indicated that the degree of differentiation,N stage,LAPTM 4 B-35 expression,and MMP-9 expression were independent prognostic indicators for patients with GC.Conclusion: LAPTM4 B-35 and MMP-9 play important roles in the aggressiveness of GC,and LAPTM4 B-35 and MMP-9 may be promising indicators for the prognosis of patients with GC.
引文
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[17]Lin J,Feng J,Jin Y,et al.Pien Tze Huang suppresses VEGF-C-mediated lymphangiogenesis in colorectal cance[J].Oncol Rep,2016,36(6):3568-3576.
[2]Yu Y,Hou L,Song H,et al.Akt/AMPK/m TOR pathway was involved in the autophagy induced by vitamin E succinate in human gastric cancer SGC-7901 cells[J].Mol Cell Biochem,2017,424(1-2):173-183.
[3]Meng F,Chen X,Song H,et al.LAPTM4B down regulation inhibits the proliferation,invasion and angiogenesis of He La cells in vitro[J].Cell Physiol Biochem,2015,37(3):890-900.
[4]Zhang H,Wei Q,Liu R,et al.Overexpression of LAPTM4B-35:a novel marker of poor prognosis of prostate cancer[J].PLo S One,2014,9(3):e91069.
[5]Chambers AF,Matrisian LM.Changing views of the role of matrix metalloproteinases in metastasis[J].J Natl Cancer Inst,1997,89(17):1260-1270.
[6]Chu D,Zhang Z,Li Y,et al.Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer[J].Int J Cancer,2011,129(4):887-895.
[7]Liu L,Xu X,Jing L,et al.Lysosomal-associated protein transmembrane 4 Beta-35 overexpression is a novel independent prognostic marker for gastric carcinoma[J].PLo S One,2015,10(2):e0118026.
[8]Yang H,Xiong F,Wei X,et al.Overexpression of LAPTM4B-35 promotes growth and metastasis of hepatocellular carcinoma in vitro and in vivo[J].Cancer Lett,2010,294(2):236-244.
[9]Zhang H,Qi S,Zhang T,et al.mi R-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression[J].Oncotarget,2015,6(8):6092-6104.
[10]Meng Y,Wang L,Chen D,et al.LAPTM4B:an oncogene in various solid tumors and its functions[J].Oncogene,2016,35(50):6359-6365.
[11]Dong X,Tamura K,Kobayashi D,et al.LAPTM4B-35 is a novel prognostic factor for glioblastoma[J].J Neurooncol,2017,132(2):295-303.
[12]Kong F,Gao F,Chen J,et al.Overexpressed LAPTM4B-35 is a risk factor for cancer recurrence and poor prognosis in non-small-cell lung cancer[J].Oncotarget,2016,7(35):56193-56199.
[13]Stetler-Stevenson WG.The role of matrix metalloproteinases in tumor invasion,metastasis and angiogenesis[J].Surg Oncol Clin N Am,2001,10(2):383-392.
[14]Du HT,Du LL,Tang XL,et al.Blockade of MMP-2 and MMP-9inhibits corneal lymphangiogenesis[J].Graefes Arch Clin Exp Ophthalmol,2017,255(8):1573-1579.
[15]Sampieri CL,de la Pe?a S,Ochoa-Lara M,et al.Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis[J].World J Gastroenterol,2010,16(12):1500-1505.
[16]Ruokolainen H,P??kk?P,Turpeenniemi-Hujanen T.Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma:a potential marker for prognosis[J].Clin Cancer Res,2004,10(9):3110-3116.
[17]Lin J,Feng J,Jin Y,et al.Pien Tze Huang suppresses VEGF-C-mediated lymphangiogenesis in colorectal cance[J].Oncol Rep,2016,36(6):3568-3576.