子宫内膜癌组织LASP1表达与预后相关性
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摘要
目的 LIM和SH3蛋白1(LIM and SH3protein 1,LASP1)作为一种肌动蛋白结合蛋白,在调控伪足延伸及细胞运动中发挥重要作用,可能作为一种转移相关蛋白参与肿瘤侵袭及转移过程。本研究分析了LASP1在子宫内膜癌组织中表达及其与预后的相关性。方法选取2012-03-02-2014-03-30湖北省中医院初诊初治子宫内膜癌患者107例,留取正常子宫内膜组织45例作为对照组,采用免疫组化法检测组织中LASP1蛋白表达,利用实时荧光定量PCR技术检测组织中LASP1基因表达,所有患者随访截止到2017-03-31,失访5例,随访率95.33%,利用Kaplan-Meier法分析子宫内膜癌组织中LASP1蛋白表达对预后的影响。结果子宫内膜癌组织中LASP1蛋白阳性表达率(71.03%)高于对照组(28.89%),差异有统计学意义,χ~2=23.178,P<0.05;子宫内膜癌组织中LASP1mRNA相对表达量为2.24±0.16,对照组LASP1mRNA相对表达量为1.14±0.11,差异有统计学意义,t=42.872,P<0.01;子宫内膜癌组织中LASP1蛋白和mRNA相对表达量与FIGO分期、分化程度、肌层浸润和淋巴结转移有关(χ~2值分别为4.929、4.873、5.319和7.896,t值分别为12.380、10.482、14.427和14.467,均P值<0.05);Kaplan-Meier生存分析结果显示,LASP1蛋白阳性表达组患者平均生存时间37.84个月,LASP1蛋白阴性表达组患者平均生存时间50.81个月,Log-rank检验差异有统计学意义,χ~2=4.315,P<0.05。结论 LASP1在子宫内膜癌组织中呈高表达,与肿瘤病理特征和预后有关。
OBJECTIVE LIM and SH3 protein 1(LASP1),as an actin-binding protein,plays an important role in the regulation of pseudopodia extension and cell movement,and may be involved in tumor invasion and metastasis as a metastasis-associated protein.This study analyzed the expression of LASP1 in endometrial carcinoma and its correlation with prognosis.METHODS Totally 107 cases of newly diagnosed and treatment patients with endometrial carcinoma in Hubei Provincial Hospital of Traditional Chinese Medicine were selected from March 2,2012 to March 30,2014.Totally 45 cases of normal endometrial tissues were taken as the control group.The expression of LASP1 protein was detected by immunohistochemistry.The expression of LASP1 gene was detected by real-time fluorescence quantitative PCR.All patients were followed up to March 31,2017.During the following up time,5 cases were lost,the follow-up rate was 95.33%.The effect of expression of LASP1 protein on the prognosis of endometrial carcinoma was analyzed by using Kaplan-Meier method.RESULTS The positive expression rate of LASP1 protein in endometrial carcinoma(71.03%)was higher than that in control group(28.89%),the difference was statistically significant,χ~2=23.178,P<0.05.The relative expression level of LASP1 mRNA in the endometrial carcinoma was 2.24±0.16,and the relative expression level of LASP1 mRNA in the control group was 1.14±0.11,the difference was statistically significant,t=42.872,P<0.01.The relative expression levels of LASP1 protein and mRNA in endometrial carcinoma were correlated with FIGO staging,differentiation,myometrial invasion and lymph node metastasis(χ~2 values were 4.929,4.873,5.319 and 7.896,t values were 12.380,10.482,14.427 and 14.467,all P<0.05).Kaplan-Meier survival analysis showed that the average survival time in LASP1 protein positive expression group was 37.84 months,and the average survival time in LASP1 protein negative expression group was 50.81 months,the Log-rank test showed the difference was statistically significant,χ~2=4.315,P=0.038.CONCLUSIONS LASP1 is highly expressed in endometrial carcinoma,and is related to the malignant pathological features and prognosis.It may be involved in tumorigenesis,invasion and metastasis process.
OBJECTIVE LIM and SH3 protein 1(LASP1),as an actin-binding protein,plays an important role in the regulation of pseudopodia extension and cell movement,and may be involved in tumor invasion and metastasis as a metastasis-associated protein.This study analyzed the expression of LASP1 in endometrial carcinoma and its correlation with prognosis.METHODS Totally 107 cases of newly diagnosed and treatment patients with endometrial carcinoma in Hubei Provincial Hospital of Traditional Chinese Medicine were selected from March 2,2012 to March 30,2014.Totally 45 cases of normal endometrial tissues were taken as the control group.The expression of LASP1 protein was detected by immunohistochemistry.The expression of LASP1 gene was detected by real-time fluorescence quantitative PCR.All patients were followed up to March 31,2017.During the following up time,5 cases were lost,the follow-up rate was 95.33%.The effect of expression of LASP1 protein on the prognosis of endometrial carcinoma was analyzed by using Kaplan-Meier method.RESULTS The positive expression rate of LASP1 protein in endometrial carcinoma(71.03%)was higher than that in control group(28.89%),the difference was statistically significant,χ~2=23.178,P<0.05.The relative expression level of LASP1 mRNA in the endometrial carcinoma was 2.24±0.16,and the relative expression level of LASP1 mRNA in the control group was 1.14±0.11,the difference was statistically significant,t=42.872,P<0.01.The relative expression levels of LASP1 protein and mRNA in endometrial carcinoma were correlated with FIGO staging,differentiation,myometrial invasion and lymph node metastasis(χ~2 values were 4.929,4.873,5.319 and 7.896,t values were 12.380,10.482,14.427 and 14.467,all P<0.05).Kaplan-Meier survival analysis showed that the average survival time in LASP1 protein positive expression group was 37.84 months,and the average survival time in LASP1 protein negative expression group was 50.81 months,the Log-rank test showed the difference was statistically significant,χ~2=4.315,P=0.038.CONCLUSIONS LASP1 is highly expressed in endometrial carcinoma,and is related to the malignant pathological features and prognosis.It may be involved in tumorigenesis,invasion and metastasis process.
引文
[1]司晓辉,孙攀兴.Septin-9在子宫内膜癌组织中的表达及意义[J].中国妇幼健康研究,2017,28(2):140-141,159.
[2]Jeppesen MM,Mogensen O,Hansen DG,et al.Detection of recurrence in early stage endometrial cancer-the role of symptoms and routine follow-up[J].Acta Oncol,2017,56(2):262-269.
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[4]Orth MF,Cazes A,Butt E,et al.An update on the LIM and SH3domain protein 1(LASP1):a versatile structural,signaling,and biomarker protein[J].Oncotarget,2015,6(1):26-42.
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[6]殷航,廖成功,王勇强,等.非小细胞肺癌组织中程序性死亡受体1的表达与表皮生长因子受体基因突变及临床病理特征和预后的关系[J].中华肿瘤杂志,2017,39(6):419-423.
[7]蒙荣钦,王阳,杜泽东,等.Wip-1基因在子宫内膜癌组织中的表达及其与细胞凋亡的关系研究[J].重庆医学,2016,45(35):4934-4937.
[8]He S,Gill BS,Heron DE,et al.Long-term outcomes using adjuvant pelvic intensity modulated radiation therapy(IMRT)for endometrial carcinoma[J].Pract Radiat Oncol,2017,7(1):19-25.
[9]Bang ML,Chen J.Roles of Nebulin family members in the heart[J].Circ J,2015,79(10):2081-2087.
[10]Butt E,Ebbing J,Bubendorf L,et al.Influence of hematuria and infection on diagnostic accuracy of urinary LASP1:a new biomarker for bladder carcinoma[J].Biomark Med,2017,11(4):347-357.
[11]Hu Z,Wang X,Cui Y,et al.LASP1in tumor and tumor microenvironment[J].Curr Mol Med,2017,17(8):541-548.
[12]Shimizu F,Shiiba M,Ogawara K,et al.Overexpression of LIMand SH3Protein 1leading to accelerated G2/M phase transition contributes to enhanced tumourigenesis in oral cancer[J/CD].PLoS One,2013,8(12):e83187.
[13]金波,高亮,李望,等.LIM和SH3蛋白1蛋白在肾透明细胞癌组织中的表达及其对肾透明细胞癌786-O细胞侵袭和迁移能力的影响[J].中华肿瘤杂志,2017,39(3):166-171.
[14]张涵,李东风,张瑛华,等.LIM和SH3蛋白1mRNA和蛋白在人胃癌组织中的表达及其临床意义[J].中华实验外科杂志,2014,31(6):1322-1324.
[15]宋佳伦,杨琦.转录因子扭曲基因表达异常在早期子宫颈癌发病中的意义及对预后的影响[J].中国妇幼健康研究,2016,27(9):1066-1068.
[16]邱瑜,黄建平,周勤仙,等.Has-miR-218靶向调控LASP1对宫颈癌HeLa细胞生长的影响[J].中国病理生理杂志,2015,31(9):1572-1577.
[17]Duvallnoelle N,Karwandyar A,Richmond A,et al.LASP-1:a nuclear hub for the UHRF1-DNMT1-G9a-Snail1complex[J].Oncogene,2016,35(9):1122-1133.
[2]Jeppesen MM,Mogensen O,Hansen DG,et al.Detection of recurrence in early stage endometrial cancer-the role of symptoms and routine follow-up[J].Acta Oncol,2017,56(2):262-269.
[3]曾靖,李艳,金滢,等.子宫内膜癌淋巴结转移的危险因素及预后分析[J].基础医学与临床,2017,37(4):454-462.
[4]Orth MF,Cazes A,Butt E,et al.An update on the LIM and SH3domain protein 1(LASP1):a versatile structural,signaling,and biomarker protein[J].Oncotarget,2015,6(1):26-42.
[5]Ruggieri V,Agriesti F,Tataranni T,et al.Paving the path for invasion:The polyedric role of LASP1in cancer[J].Tumour Biol,2017,39(6):1-6.
[6]殷航,廖成功,王勇强,等.非小细胞肺癌组织中程序性死亡受体1的表达与表皮生长因子受体基因突变及临床病理特征和预后的关系[J].中华肿瘤杂志,2017,39(6):419-423.
[7]蒙荣钦,王阳,杜泽东,等.Wip-1基因在子宫内膜癌组织中的表达及其与细胞凋亡的关系研究[J].重庆医学,2016,45(35):4934-4937.
[8]He S,Gill BS,Heron DE,et al.Long-term outcomes using adjuvant pelvic intensity modulated radiation therapy(IMRT)for endometrial carcinoma[J].Pract Radiat Oncol,2017,7(1):19-25.
[9]Bang ML,Chen J.Roles of Nebulin family members in the heart[J].Circ J,2015,79(10):2081-2087.
[10]Butt E,Ebbing J,Bubendorf L,et al.Influence of hematuria and infection on diagnostic accuracy of urinary LASP1:a new biomarker for bladder carcinoma[J].Biomark Med,2017,11(4):347-357.
[11]Hu Z,Wang X,Cui Y,et al.LASP1in tumor and tumor microenvironment[J].Curr Mol Med,2017,17(8):541-548.
[12]Shimizu F,Shiiba M,Ogawara K,et al.Overexpression of LIMand SH3Protein 1leading to accelerated G2/M phase transition contributes to enhanced tumourigenesis in oral cancer[J/CD].PLoS One,2013,8(12):e83187.
[13]金波,高亮,李望,等.LIM和SH3蛋白1蛋白在肾透明细胞癌组织中的表达及其对肾透明细胞癌786-O细胞侵袭和迁移能力的影响[J].中华肿瘤杂志,2017,39(3):166-171.
[14]张涵,李东风,张瑛华,等.LIM和SH3蛋白1mRNA和蛋白在人胃癌组织中的表达及其临床意义[J].中华实验外科杂志,2014,31(6):1322-1324.
[15]宋佳伦,杨琦.转录因子扭曲基因表达异常在早期子宫颈癌发病中的意义及对预后的影响[J].中国妇幼健康研究,2016,27(9):1066-1068.
[16]邱瑜,黄建平,周勤仙,等.Has-miR-218靶向调控LASP1对宫颈癌HeLa细胞生长的影响[J].中国病理生理杂志,2015,31(9):1572-1577.
[17]Duvallnoelle N,Karwandyar A,Richmond A,et al.LASP-1:a nuclear hub for the UHRF1-DNMT1-G9a-Snail1complex[J].Oncogene,2016,35(9):1122-1133.