β-连环蛋白和生存素在老年结直肠腺癌患者中的表达及其意义
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摘要
目的检测β-连环蛋白(β-catenin)和生存素(survivin)蛋白在老年结直肠腺癌组织中的表达,分析其与老年结直肠腺癌患者性别、淋巴结转移以及肿瘤-淋巴结-转移(TNM)分期之间的关系,探讨β-catenin和survivin蛋白表达的相关性。方法收集2015年1月至2017年12月在长治医学院附属和平医院及和济医院进行手术切除治疗的结直肠腺癌患者50例,将外科手术切除后的标本分为2组:癌组织组和正常组织组(距离癌组织边缘>2 cm,病理检测结果正常),每组50例。采用免疫组织化学法检测β-catenin和survivin蛋白表达。采用SPSS 22.0软件进行数据处理。组间比较采用Mann-Whitney U秩和检验。Spearman相关分析β-catenin蛋白表达与survivin蛋白表达的相关性。结果β-catenin蛋白在结直肠腺癌细胞膜、细胞浆及细胞核呈阳性表达,在老年癌组织组的阳性表达率显著高于正常组织组(64.0%vs 0.0%,P<0.001),其表达与性别无关(P>0.05),与淋巴结转移及TNM分期相关(P<0.05)。survivin蛋白在结直肠腺癌细胞核呈阳性表达,在老年癌组织组的阳性表达率显著高于正常组织组(54.0%vs 0.0%,P<0.001),其表达与性别、TNM分期无关(P>0.05),与淋巴结转移相关(P<0.05)。Spearman相关分析统计结果显示,老年结直肠腺癌患者的β-catenin蛋白表达与survivin蛋白表达呈显著正相关(r=0.645,P<0.001)。结论β-catenin和survivin蛋白均参与老年结直肠腺癌的发生发展,可能共同促进老年结直肠癌的进展。
Objective To detect the expression of β-catenin and survivin proteins in colorectal adenocarcinoma tissues of elderly patients, and investigate the correlation of their expression with gender, lymph node metastasis and tumor-lymph node-metastasis(TNM) stage. Methods A total of 50 colorectal adenocarcinoma patients who underwent surgical resection in our hospital from January 2015 to December 2017 were recruited in this study. The obtained specimens were divided into cancer tissue group(n=50) and normal tissue group(n=50, 2 cm away from the edge of the colorectal cancer mass, with microscopically normal tissue structure). The expression of β-catenin and survivin were detected by immunohistochemistry. SPSS statistics 22.0 was used for data analysis. Mann-Whitney U rank test was employed for comparison between 2 groups. Spearman test was applied to analyze the correlation of protein expression between β-catenin and survivin. Results β-catenin was mainly expressed in the membrane, cytoplasm and nucleus of colorectal adenocarcinoma cells, and its expression level was significantly higher in cancer tissues than normal tissues(64.0% vs 0.0%, P<0.05). Its expression was not related to gender(P>0.05), but was to lymph node metastasis and TNM stage(P<0.001). Survivin was located in the nuclei of colorectal cancer cells, and its expression was markedly higher in the colorectal cancer tissues than normal tissues(54.0% vs 0.0%, P<0.001). Its level had correlation with lymphatic invasion(P<0.05) but not with gender and TNM stage(P>0.05). Spearman correlation analysis showed that the protein expression of β-catenin was positively correlated to that of survivin in the elderly patients with colorectal adenocarcinoma(r=0.645, P<0.001). Conclusion Both of β-catenin and survivinare involved in the occurrence and development of colorectal cancer in elderly patients, and they may jointly promote its progression.
Objective To detect the expression of β-catenin and survivin proteins in colorectal adenocarcinoma tissues of elderly patients, and investigate the correlation of their expression with gender, lymph node metastasis and tumor-lymph node-metastasis(TNM) stage. Methods A total of 50 colorectal adenocarcinoma patients who underwent surgical resection in our hospital from January 2015 to December 2017 were recruited in this study. The obtained specimens were divided into cancer tissue group(n=50) and normal tissue group(n=50, 2 cm away from the edge of the colorectal cancer mass, with microscopically normal tissue structure). The expression of β-catenin and survivin were detected by immunohistochemistry. SPSS statistics 22.0 was used for data analysis. Mann-Whitney U rank test was employed for comparison between 2 groups. Spearman test was applied to analyze the correlation of protein expression between β-catenin and survivin. Results β-catenin was mainly expressed in the membrane, cytoplasm and nucleus of colorectal adenocarcinoma cells, and its expression level was significantly higher in cancer tissues than normal tissues(64.0% vs 0.0%, P<0.05). Its expression was not related to gender(P>0.05), but was to lymph node metastasis and TNM stage(P<0.001). Survivin was located in the nuclei of colorectal cancer cells, and its expression was markedly higher in the colorectal cancer tissues than normal tissues(54.0% vs 0.0%, P<0.001). Its level had correlation with lymphatic invasion(P<0.05) but not with gender and TNM stage(P>0.05). Spearman correlation analysis showed that the protein expression of β-catenin was positively correlated to that of survivin in the elderly patients with colorectal adenocarcinoma(r=0.645, P<0.001). Conclusion Both of β-catenin and survivinare involved in the occurrence and development of colorectal cancer in elderly patients, and they may jointly promote its progression.
引文
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[2] Behrens J,Lustig B.The Wnt connection to tumorigenesis[J].Int J Dev Biol,2004,48(5-6):477-487.DOI:10.1387/ijdb.041815jb.
[3] 常建兰,李祖国,王晓燕,等.P53、malat 1、ki-67和β-catenin基因mRNA检测在大肠癌分子诊断中的意义[J].世界华人消化杂志,2008,16(34):3849-3854.DOI:10.11569/wcjd.v16.i34.3849.Chang JL,Li ZG,Wang XY,et al.Detection of P53,malat 1,ki-67 and β-catenin mRNA expression and its significance in molecular diagnosis of colorectal carcinoma[J].World Chin J Dig,2008,16(34):3849-3854.DOI:10.11569/wcjd.v16.i34.3849.
[4] Ma H,Nguyen C,Lee KS,et al.Differential roles for the coactivators CBP and p300 on TCF/beta-catenin-mediated survivin gene expression[J].Oncogene,2005,24(22):3619-3631.DOI:10.1038/sj.onc.1208433.
[5] Kanwar JR,Kamalapuram SK,Kanwar RK.Targeting survivin in cancer:the cell-signalling perspective[J].Drug Discov Today,2011,16(11-12):485-494.DOI:10.1016/j.drudis.2011.04.001.
[6] Faversani A,Vaira V,Moro GP,et al.Survivin family proteins as novel molecular determinants of doxorubicin resistance in organotypic human breast tumors[J].Breast Cancer Res,2014,16(3):R55.DOI:10.1186/bcr3666.
[7] Wang D,Jiao C,Zhu Y,et al.Activation of CXCL12/CXCR4 renders colorectal cancer cells less sensitive to radiotherapy via up-regulating the expression of survivin[J].Exp Biol Med (Maywood),2017,242(4):429-435.DOI:10.1177/1535370216675068.
[8] 姚宏伟,吴鸿伟,刘荫华.美国癌症联合委员会第八版结直肠癌分期更新及其“预后和预测”评价体系[J].中华胃肠外科杂志,2017,20(1):24-27.Yao HW,Wu HW,Liu YH.A predicted and prognostic evaluation analysis using the 8th edition of American Joint Committee on Cancer(AJCC) staging system for colorectal cancer[J].Chin J Gastrointest Surg,2017,20(1):24-27.
[9] 姜素,田文艳,闫晔,等.迁移侵袭抑制蛋白和p21活化激酶1在子宫内膜癌中的表达及其临床意义[J].中华肿瘤杂志,2018,40(5):359-364.DOI:10.3760/cma.j.issn.0253-3766.2018.05.008.Jiang S,Tian WY,Yan Y,et al.Expression and clinical significance of MIIP and PAK1 in endometrial carcinoma[J].Chin J Oncol,2018,40(5):359-364.DOI:10.3760/cma.j.issn.0253-3766.2018.05.008.
[10] 陈亚君,张维璐,何玉红.结直肠癌高危因素研究进展[J].中华老年多器官疾病杂志,2018,17(9):704-707.DOI:10.11915/j.issn.1671-5403.2018.09.162.Chen YJ,Zhang WL,He YH.Research progress in risk factors for colorectal cancer[J].Chin J Mult Organ Dis Elderly,2018,17(9):704-707.DOI:10.11915/j.issn.1671-5403.2018.09.162.
[11] Nazemalhosseini Mojarad E,Kashfi SM,Mirtalebi H,et al.Prognostic significance of nuclear beta-catenin expression in patients with colorectal cancer from Iran[J].Iran Red Crescent Med J,2015,17(7):e22324.DOI:10.5812/ircmj.22324v2.
[12] Serafino A,Moroni N,Zonfrillo M,et al.Wnt-pathway components as predictive markers useful for diagnosis,prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer[J].Oncotarget,2014,5(4):978-992.DOI:10.18632/oncotarget.1571.
[13] Hao L,Zhao Y,Wang Z,et al.Expression and clinical significance of SALL 4 and beta-catenin in colorectal cancer[J].J Mol Histol,2016,47(2):117-128.DOI:10.1007/s10735-016-9656-5.
[14] Fulda S,Vucic D.Targeting IAP proteins for therapeutic intervention in cancer[J].Nat Rev Drug Discov,2012,11(2):109-124.DOI:10.1038/nrd3627.
[15] Asanuma K,Tsuji N,Endoh T,et al.Survivin enhances Fas ligand expression via up-regulation of specificity protein 1-mediated gene transcription in colon cancer cells[J].J Immunol,2004,172(6):3922-3929.DOI:10.4049/jimmunol.172.6.3922.
[16] Shamsabadi FT,Eidgahi MR,Mehrbod P,et al.Survivin,a promising gene for targeted cancer treatment[J].Asian Pac J Cancer Prev,2016,17(8):3711-3719.
[17] Lee SC,Kim OH,Lee SK,et al.IWR-1 inhibits epithelial-mesenchymal transition of colorectal cancer cells through suppres-sing Wnt/β-catenin signaling as well as survivin expression[J].Oncotarget,2015,6(29):27146-27159.DOI:10.18632/oncotarget.4354.