结肠癌组织中WWP1、C-myc的表达及临床意义
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摘要
目的检测WWP1、C-myc在结肠癌组织中的表达,探究其与结肠癌患者病情进展、预后的关系。方法采用免疫组织化学法检测河北北方学院附属第一医院收治的135例结肠癌患者的癌组织、癌旁正常组织中WWP1、C-myc蛋白表达情况,分析癌组织中WWP1、C-myc表达与患者临床病理参数、无进展生存期(PFS)及总生存期(OS)的关系,用Cox回归分析结肠癌预后的危险因素。结果结肠癌组织WWP1、C-myc蛋白阳性表达率高于癌旁正常组织(P<0.05);结肠癌组织WWP1、C-myc蛋白表达受Dukes分期、肿瘤浸润深度及淋巴结转移的影响较大(P<0.05);Kaplan-Meier生存分析表明,结肠癌组织WWP1、C-myc阳性表达患者术后PFS、OS较短(P<0.05);Cox回归分析结果显示,分化程度[RlR=29.203(95%CI:4.759,179.192)]、肿瘤Dukes分期[RlR=16.817(95%CI:2.765,102.271)]、浸润深度[RlR=3.285(95%CI:1.450,7.442)]、淋巴结转移[RlR=18.723(95%CI:4.131,84.861)]、WWP1表达[RlR=11.344(95%CI:3.472,37.060)]及C-myc表达[RlR=12.873(95%CI:3.092,53.592)]为影响结肠癌患者预后的独立危险因素。结论结肠癌组织中WWP1、C-myc异常高表达,且与患者病情恶性进展、预后不良关系密切,WWP1、C-myc可作为预测结肠癌患者预后的参考指标。
Objective To determine the expression of WW domain containing E3 ubiquitin protein ligase 1(WWP1)and oncogene C-myc in colon cancer tissues, and explore their correlation with disease progression and prognosis of colon cancer. Methods Immunohistochemical method was used to detect the expression of WWP1 and C-myc protein in cancer tissues and adjacent cancer normal tissues from 135 patients treated in our hospital. The relationship between WWP1 and C-myc expression and clinicopathological parameters, progression free survival(PFS) and total survival(OS) were analyzed. Risk factors for prognosis of colon cancer were analyzed by Cox regression analysis. Results In colon cancer tissues, the positive expression rates of WWP1 and C-myc protein were statistically higher than those in adjacent cancer normal tissues(P < 0.05). In colon cancer tissues, the expressions of WWP1 and C-myc in colon cancer tissues were significantly affected by Dukes stage, depth of invasion and lymph node metastasis(P < 0.05). The analysis results of Kaplan-Meier survival curves showed that patients with positive expression of WWP1 and C-myc ended up with shorter PFS and OS(P < 0.05). Cox regression analysis showed that tumor differentiation [Rl^R=29.203,(95% CI: 4.759, 179.192)] Dukes stage [RlR=16.817,(95% CI: 2.765, 102.271)], depth of invasion [Rl^R=3.285,(95% CI: 1.450, 7.442)], lymph node metastasis[RlR=18.723,(95% CI: 4.131, 84.861)] WWP1 expression [RlR=11.344,(95% CI: 3.472, 37.060)] and C-myc expression[RlR=12.873,(95% CI: 3.092, 53.592)] were independent risk factors for prognosis of colon cancer patients. Conclusions The abnormal high expression of WWP1 and C-myc in colon cancer tissues are closely related to malignant degree and poor prognosis of colon cancer. WWP1 and C-myc have potential value as a prognostic indicator for colon cancer patients.
Objective To determine the expression of WW domain containing E3 ubiquitin protein ligase 1(WWP1)and oncogene C-myc in colon cancer tissues, and explore their correlation with disease progression and prognosis of colon cancer. Methods Immunohistochemical method was used to detect the expression of WWP1 and C-myc protein in cancer tissues and adjacent cancer normal tissues from 135 patients treated in our hospital. The relationship between WWP1 and C-myc expression and clinicopathological parameters, progression free survival(PFS) and total survival(OS) were analyzed. Risk factors for prognosis of colon cancer were analyzed by Cox regression analysis. Results In colon cancer tissues, the positive expression rates of WWP1 and C-myc protein were statistically higher than those in adjacent cancer normal tissues(P < 0.05). In colon cancer tissues, the expressions of WWP1 and C-myc in colon cancer tissues were significantly affected by Dukes stage, depth of invasion and lymph node metastasis(P < 0.05). The analysis results of Kaplan-Meier survival curves showed that patients with positive expression of WWP1 and C-myc ended up with shorter PFS and OS(P < 0.05). Cox regression analysis showed that tumor differentiation [Rl^R=29.203,(95% CI: 4.759, 179.192)] Dukes stage [RlR=16.817,(95% CI: 2.765, 102.271)], depth of invasion [Rl^R=3.285,(95% CI: 1.450, 7.442)], lymph node metastasis[RlR=18.723,(95% CI: 4.131, 84.861)] WWP1 expression [RlR=11.344,(95% CI: 3.472, 37.060)] and C-myc expression[RlR=12.873,(95% CI: 3.092, 53.592)] were independent risk factors for prognosis of colon cancer patients. Conclusions The abnormal high expression of WWP1 and C-myc in colon cancer tissues are closely related to malignant degree and poor prognosis of colon cancer. WWP1 and C-myc have potential value as a prognostic indicator for colon cancer patients.
引文
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[13]LIU J,LI X,ZHANG H,et al.Ubiquitin E3 ligase itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins[J].Bone Joint Res,2017,6(3):154-161.
[14]ZHAO D,ZHI X,ZHOU Z,et al.TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis[J].Carcinogenesis,2012,33(1):59-67.
[15]SUBIK K,SHU L,WU C,et al.The ubiquitin E3 ligase WWP1decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis[J].Bone,2012,50(4):813-823.
[16]LI X X,SHI L,ZHOU X J,et al.The role of c-Myc-RBM38 loop in the growth suppression in breast cancer[J].J Exp Clin Cancer Res,2017,36(1):49.
[17]杨先国,戈伟,王建国,等.非小细胞肺癌中c-myc表达与其临床特征的相关性分析[J].实用癌症杂志,2016,31(9):1393-1395.
[18]王宁,朴成哲,孟晓娜.Runx3和c-Myc蛋白在TGF-β抑制MG-63细胞增殖中作用[J].解剖科学进展,2018,24(1):65-68.
[19]CHEN X M,BAI Y,ZHONG Y J,et al.Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7αand HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549[J].PLoS One,2013,8(11):e79201.
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[21]唐文武,莫灿坤,吴秀兰.无籽沙糖桔E3泛素连接酶U-box基因的克隆及表达分析[J].江西农业大学学报,2018,40(2):383-388.
[2]孙小莉,曹晓侠,丁晓明,等.宝鸡地区80例结肠癌患者发病危险因素研究[J].现代生物医学进展,2016,16(23):4505-4507.
[3]刘清安,肖泽民,郭敏,等.多学科协作模式对结肠癌患者住院费用,平均住院日,并发症发生率的影响[J].中国现代医学杂志,2016,26(13):138-140.
[4]YEUNG B,HO K C,YANG X.WWP1 E3 ligase targets LATS1for ubiquitin-mediated degradation in breast cancer cells[J].PLoSOne,2013,8(4):e61027.
[5]王娟.硼替佐米调控泛素连接酶E3家族成员表达水平对前列腺癌抑制作用的分析[D].石家庄:河北医科大学,2015,13(20):25-27.
[6]刘海青,施晓,杜玲,等.癌基因K-ras及C-myc在宫颈癌中的表达及临床意义[J].中国妇幼保健,2017,32(9):2007-2010.
[7]WATANABE J,ISHIBE A,SUWA Y,et al.Real-time indocyanine green fluorescence imaging-guided laparoscopic right hemicolectomy in hepatic flexural colon cancer[J].Dis Colon Rectum,2018,61(11):1333-1334.
[8]SOAVE C L,GUERIN T,LIU J,et al.Targeting the ubiquitinproteasome system for cancer treatment:discovering novel inhibitors from nature and drug repurposing[J].Cancer Metastasis Rev,2017,36(4):717-736.
[9]AO N,CHEN Q,LIU G.The small molecules targeting ubiquitinproteasome system for cancer therapy[J].Comb Chem High Throughput Screen,2017,20(5):403-413.
[10]TSUKAMOTO S.Search for inhibitors of the ubiquitinproteasome system from natural sources for cancer therapy[J].Chem Pharm Bull(Tokyo),2016,64(2):112-118.
[11]LI Q,LI Z,WEI S,et al.Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domaincontaining E3 ubiquitin protein ligase 1 in gastric cancer[J].J Exp Clin Cancer Res,2017,36(1):59.
[12]ZHANG L,WU Z,MA Z,et al.WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma[J].Tumour Biol,2015,36(2):787-798.
[13]LIU J,LI X,ZHANG H,et al.Ubiquitin E3 ligase itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins[J].Bone Joint Res,2017,6(3):154-161.
[14]ZHAO D,ZHI X,ZHOU Z,et al.TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis[J].Carcinogenesis,2012,33(1):59-67.
[15]SUBIK K,SHU L,WU C,et al.The ubiquitin E3 ligase WWP1decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis[J].Bone,2012,50(4):813-823.
[16]LI X X,SHI L,ZHOU X J,et al.The role of c-Myc-RBM38 loop in the growth suppression in breast cancer[J].J Exp Clin Cancer Res,2017,36(1):49.
[17]杨先国,戈伟,王建国,等.非小细胞肺癌中c-myc表达与其临床特征的相关性分析[J].实用癌症杂志,2016,31(9):1393-1395.
[18]王宁,朴成哲,孟晓娜.Runx3和c-Myc蛋白在TGF-β抑制MG-63细胞增殖中作用[J].解剖科学进展,2018,24(1):65-68.
[19]CHEN X M,BAI Y,ZHONG Y J,et al.Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7αand HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549[J].PLoS One,2013,8(11):e79201.
[20]HEIDELBERGER J B,VOIGT A,BORISOVA M E,et al.Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function[J].EMBO Rep,2018,19(4):e44754.
[21]唐文武,莫灿坤,吴秀兰.无籽沙糖桔E3泛素连接酶U-box基因的克隆及表达分析[J].江西农业大学学报,2018,40(2):383-388.