乳腺癌组织中ELMO3,FOXK1的表达及其临床意义
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摘要
目的:检测乳腺癌组织中吞噬和运动蛋白3(engulfment and cell mobility 3,ELMO3)、叉头框转录因子1(forkhead box k1,FOXK1)的表达情况,并探讨两者在乳腺癌组织中表达的相关性及与乳腺癌患者临床病理参数、预后的关系。方法:收集2013年1月至2018年1月惠州市第三人民医院乳腺癌患者手术标本80例,应用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)和免疫组织化学检测乳腺癌组织及癌旁组织中ELMO3与FOXK1的表达情况;并分析乳腺癌组织中ELMO3与FOXK1表达的相关性,及其的表达与乳腺癌患者临床病理参数、预后的关系。结果:qRT-PCR检测ELMO3mRNA,FOXK1mRNA在乳腺癌组织中表达分别为1.16±0.48,1.34±0.60,在癌旁组织中表达分别为0.81±0.36,0.95±0.49;乳腺癌组织中ELMO3与FOXK1表达水平均高于癌旁组织(均P<0.05),且乳腺癌组织中ELMO3与FOXK1的表达呈正相关(r=0.423,P=0.037)。免疫组织化学检测EL MO3与FOX K1在乳腺癌组织中阳性表达分别为58例(72.52%),6 2例(7 7. 5 0%),在癌旁组织中阳性表达分别为2 8例(3 5. 0 0%), 2 9例(3 6. 2 5%),乳腺癌组织中ELMO3与FOXK1阳性表达率均高于癌旁组织(均P<0.05)。ELMO3与肿瘤TNM分期、淋巴结转移显著相关,FOXK1与肿瘤组织TNM分期、淋巴结转移和组织分级显著相关(均P<0.05)。KaplanMeier生存曲线分析显示乳腺癌组织中ELMO3与FOXK1高表达患者生存期较短。结论:乳腺癌组织中ELMO3与FOXK1呈高表达,并与肿瘤发生发展及预后有关。ELMO3与FOXK1在乳腺癌组织中表达呈正相关,可能协同参与了乳腺癌的发生发展。ELMO3与FOXK1具有作为乳腺癌新的标志物、治疗靶标及评估预后的潜在价值。
Objective: To detect the expression of engulfment and cell mobility 3(ELMO3) and forkhead box k1(FOXK1)in breast cancer tissues, and to explore the correlation between their expression in breast cancer tissues, and relationship between the level of ELMO3, FOXK1 expression with clinical pathological parameters and prognosis of breast cancer patients. Methods: Eighty patients with breast cancer patients from January 2013 to January 2018 were enrolled. The expressions of ELMO3, FOXK1 in breast cancer tissues and adjacent tissues were detected by qRT-PCR and immunohistochemistry. Correlation between expression of ELMO3 and FOXK1 in cancer tissues were analysis, and the relationship between the expression of ELMO3, FOXK1 and clinicopathological parameters, prognosis of breast cancer patients was analysis respectively. Results: The expressions of ELMO3 mRNA and FOXK1 mRNA in breast cancer tissues were 1.16±0.48, 1.34±0.60, respectively, and which in adjacent tissues were 0.81±0.36, 0.95±0.49. The expression level ELMO3 and FOXK1 was higher in breast cancer tissues than that in adjacent tissues(P<0.05), and there was a positive correlation between ELMO3 and FOXK1 expression in breast cancer tissues(r=0.423, P=0.037). Immunohistochemistry detected the positive expressions of ELMO3 and FOXK1 in breast cancer tissues were 58(72.52%) and 62(77.50%), respectively. The positive expressions in the adjacent tissues were 28(35.00%) and 29(36.25%), respectively. The positive expression rates of ELMO3 and FOXK1 in breast cancer tissues were higher than that in adjacent tissues(P<0.05). ELMO3 was significantly associated with tumor TNM stage and lymph node metastasis. FOXK1 was significantly associated with tumor tissue TNM stage, lymph node metastasis and tissue grade(P<0.05). Kaplan-Meier survival curve analysis patients with high expression of ELMO3 and FOXK1 in breast cancer tissues had shorter survival time.Conclusion: ELMO3 and FOXK1 are highly expressed in breast cancer tissues and are associated with tumor development and prognosis. The expression of ELMO3 and FOXK1 was positively correlated in breast cancer tissues, which may be involved in the development of breast cancer. ELMO3 and FOXK1 have potential value as new markers, therapeutic targets and prognosis for breast cancer.
Objective: To detect the expression of engulfment and cell mobility 3(ELMO3) and forkhead box k1(FOXK1)in breast cancer tissues, and to explore the correlation between their expression in breast cancer tissues, and relationship between the level of ELMO3, FOXK1 expression with clinical pathological parameters and prognosis of breast cancer patients. Methods: Eighty patients with breast cancer patients from January 2013 to January 2018 were enrolled. The expressions of ELMO3, FOXK1 in breast cancer tissues and adjacent tissues were detected by qRT-PCR and immunohistochemistry. Correlation between expression of ELMO3 and FOXK1 in cancer tissues were analysis, and the relationship between the expression of ELMO3, FOXK1 and clinicopathological parameters, prognosis of breast cancer patients was analysis respectively. Results: The expressions of ELMO3 mRNA and FOXK1 mRNA in breast cancer tissues were 1.16±0.48, 1.34±0.60, respectively, and which in adjacent tissues were 0.81±0.36, 0.95±0.49. The expression level ELMO3 and FOXK1 was higher in breast cancer tissues than that in adjacent tissues(P<0.05), and there was a positive correlation between ELMO3 and FOXK1 expression in breast cancer tissues(r=0.423, P=0.037). Immunohistochemistry detected the positive expressions of ELMO3 and FOXK1 in breast cancer tissues were 58(72.52%) and 62(77.50%), respectively. The positive expressions in the adjacent tissues were 28(35.00%) and 29(36.25%), respectively. The positive expression rates of ELMO3 and FOXK1 in breast cancer tissues were higher than that in adjacent tissues(P<0.05). ELMO3 was significantly associated with tumor TNM stage and lymph node metastasis. FOXK1 was significantly associated with tumor tissue TNM stage, lymph node metastasis and tissue grade(P<0.05). Kaplan-Meier survival curve analysis patients with high expression of ELMO3 and FOXK1 in breast cancer tissues had shorter survival time.Conclusion: ELMO3 and FOXK1 are highly expressed in breast cancer tissues and are associated with tumor development and prognosis. The expression of ELMO3 and FOXK1 was positively correlated in breast cancer tissues, which may be involved in the development of breast cancer. ELMO3 and FOXK1 have potential value as new markers, therapeutic targets and prognosis for breast cancer.
引文
1.Siegel RL,Miller KD.Cancer statistics,2015[J].CA Cancer J Clin,2015,65(1):5-29.
2.DeSantis CE,Ma J,Goding Sauer A,et al.Breast cancer statistics,2017,racial disparity in mortality by state[J].CA Cancer J Clin,2017,67(6):439-448.
3.Zeng H,Zheng R,Guo Y,et al.Cancer survival in China,2003-2005:a population-based study[J].Int J Cancer,2015,136(8):1921-1930.
4.中国抗癌协会乳腺癌专业委员会.中国晚期乳腺癌临床诊疗专家共识(2018版)[J].中华肿瘤杂志,2018,40(9):703-713.Chinese Anti-Cancer Association,Committee of Breast Cancer Society.Chinese expert consensus on the clinical diagnosis and treatment of advanced breast carcinoma(2018 edition)[J].Chinese Journal of Oncology,2018,40(9):703-713.
5.Li J,Han X.Adipocytokines and breast cancer[J].Curr Probl Cancer,2018,42(2):208-214.
6.Bertucci F,Birnbaum D.Reasons for breast cancer heterogeneity[J].JBiol,2008,7(2):6.
7.Haymerle G,Kadletz L,Wiebringhaus R,et al.ELMO3 predicts poor outcome in T1 laryngeal cancer[J].Clin Otolaryngol,2017,42(6):1181-1186.
8.Kadletz L,Heiduschka G,Wiebringhaus R,et al.ELMO3 expression indicates a poor prognosis in head and neck squamous cell carcinomaa short report[J].Cell Oncol(Dordr),2017,40(2):193-198.
9.倪路,赵志强,高越,等.FOXK1对肝癌高转移细胞系Huh7侵袭和迁移能力的影响[J].中国癌症防治杂志,2018,10(4):286-289.NI Lu,ZHAO Zhiqiang,GAO Yue,et al.Effect of FOXK1 on the invasion and migration of hepatocellular carcinoma cell line Huh7[J].Chinese Journal of Oncology Prevention and Treatment,2018,10(4):286-289.
10.Shi X,Seldin DC.Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors[J].Biochem J,2012,446(3):349-357.
11.Siegel RL,Miller KD.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
12.Tysarowski A.Quality and practical aspects of pathological and molecular diagnostics in metastatic colorectal cancer(mCRC)[J].Contemp Oncol(Pozn),2018,22(2):75-85.
13.Song Q,Huang R,Li J,et al.The diverse distribution of risk factors between breast cancer subtypes of ER,PR and HER2:a 10-year retrospective multi-center study in China[J].PLoS One,2013,8(8):e72175.
14.Curigliano G.Maximizing the clinical benefit of anthracyclines in addition to taxanes in the adjuvant treatment of early breast cancer[J].J Clin Oncol,2017,35(23):2600-2603.
15.Hernández-Vásquez MN,Adame-García SR,Hamoud N,et al.Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock[J].J Biol Chem,2017,292(29):12178-12191.
16.Shi L,Zhang B,Sun X,et al.CC chemokine ligand 18(CCL18)promotes migration and invasion of lung cancer cells by binding to Nir1through Nir1-ELMO1/DOC180 signaling pathway[J].Mol Carcinog,2016,55(12):2051-2062.
17.Li W,Xiong X,Abdalla A,et al.HGF-induced formation of the MET-AXL-ELMO2-DOCK180 complex promotes RAC1 activation,receptor clustering,and cancer cell migration and invasion[J].J Biol Chem,2018,293(40):15397-15418.
18.Michaelsen SR,Aslan D,Urup T,et al.DNA methylation levels of the ELMO gene promoter CpG islands in human glioblastomas[J].Int JMol Sci,2018,19(3):33-42.
19.Kotowski U,Kadletz L,Schneider S,et al.ELMO3-a negative prognostic marker in minor salivary gland carcinoma[J].Pathol Oncol Res,2018,[Epub ahead of print].
20.Hu Y,Yu Q,Zhong Y,et al.Silencing ELMO3 Inhibits the growth,invasion,and metastasis of gastric cancer[J].Biomed Res Int,2018,2018:3764032.
21.Peng HY,Yu QF,Shen W,et al.Knockdown of ELMO3 suppresses growth,invasion and metastasis of colorectal cancer[J].Int J Mol Sci,2016,17(12):2119.
22.Gaudet J.Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4[J].Science,2002,295(5556):821-825.
23.Cui H,Gao Q,Zhang L,et al.Knockdown of FOXK1 suppresses liver cancer cell viability by inhibiting glycolysis[J].Life Sci,2018,213:66-73.
24.Chen F,Xiong W,Dou K.Knockdown of FOXK1 suppresses proliferation,migration,and invasion in prostate cancer cells[J].Oncol Res,2017,25(8):1261-1267.
25.Li L,Gong M,Zhao Y,et al.FOXK1 facilitates cell proliferation through regulating the expression of p21,and promotes metastasis in ovarian cancer[J].Oncotarget,2017,8(41):70441-70451.
26.Huang X,Xiang L,Li Y,et al.Snail/FOXK1/Cyr61 signaling axis regulates the epithelial-mesenchymal transition and metastasis in colorectal cancer[J].Cell Physiol Biochem,2018,47(2):590-603.
27.Chen D,Wang K,Li X,et al.FOXK1 plays an oncogenic role in the development of esophageal cancer[J].Biochem Biophys Res Commun,2017,494(1/2):88-94.
2.DeSantis CE,Ma J,Goding Sauer A,et al.Breast cancer statistics,2017,racial disparity in mortality by state[J].CA Cancer J Clin,2017,67(6):439-448.
3.Zeng H,Zheng R,Guo Y,et al.Cancer survival in China,2003-2005:a population-based study[J].Int J Cancer,2015,136(8):1921-1930.
4.中国抗癌协会乳腺癌专业委员会.中国晚期乳腺癌临床诊疗专家共识(2018版)[J].中华肿瘤杂志,2018,40(9):703-713.Chinese Anti-Cancer Association,Committee of Breast Cancer Society.Chinese expert consensus on the clinical diagnosis and treatment of advanced breast carcinoma(2018 edition)[J].Chinese Journal of Oncology,2018,40(9):703-713.
5.Li J,Han X.Adipocytokines and breast cancer[J].Curr Probl Cancer,2018,42(2):208-214.
6.Bertucci F,Birnbaum D.Reasons for breast cancer heterogeneity[J].JBiol,2008,7(2):6.
7.Haymerle G,Kadletz L,Wiebringhaus R,et al.ELMO3 predicts poor outcome in T1 laryngeal cancer[J].Clin Otolaryngol,2017,42(6):1181-1186.
8.Kadletz L,Heiduschka G,Wiebringhaus R,et al.ELMO3 expression indicates a poor prognosis in head and neck squamous cell carcinomaa short report[J].Cell Oncol(Dordr),2017,40(2):193-198.
9.倪路,赵志强,高越,等.FOXK1对肝癌高转移细胞系Huh7侵袭和迁移能力的影响[J].中国癌症防治杂志,2018,10(4):286-289.NI Lu,ZHAO Zhiqiang,GAO Yue,et al.Effect of FOXK1 on the invasion and migration of hepatocellular carcinoma cell line Huh7[J].Chinese Journal of Oncology Prevention and Treatment,2018,10(4):286-289.
10.Shi X,Seldin DC.Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors[J].Biochem J,2012,446(3):349-357.
11.Siegel RL,Miller KD.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
12.Tysarowski A.Quality and practical aspects of pathological and molecular diagnostics in metastatic colorectal cancer(mCRC)[J].Contemp Oncol(Pozn),2018,22(2):75-85.
13.Song Q,Huang R,Li J,et al.The diverse distribution of risk factors between breast cancer subtypes of ER,PR and HER2:a 10-year retrospective multi-center study in China[J].PLoS One,2013,8(8):e72175.
14.Curigliano G.Maximizing the clinical benefit of anthracyclines in addition to taxanes in the adjuvant treatment of early breast cancer[J].J Clin Oncol,2017,35(23):2600-2603.
15.Hernández-Vásquez MN,Adame-García SR,Hamoud N,et al.Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock[J].J Biol Chem,2017,292(29):12178-12191.
16.Shi L,Zhang B,Sun X,et al.CC chemokine ligand 18(CCL18)promotes migration and invasion of lung cancer cells by binding to Nir1through Nir1-ELMO1/DOC180 signaling pathway[J].Mol Carcinog,2016,55(12):2051-2062.
17.Li W,Xiong X,Abdalla A,et al.HGF-induced formation of the MET-AXL-ELMO2-DOCK180 complex promotes RAC1 activation,receptor clustering,and cancer cell migration and invasion[J].J Biol Chem,2018,293(40):15397-15418.
18.Michaelsen SR,Aslan D,Urup T,et al.DNA methylation levels of the ELMO gene promoter CpG islands in human glioblastomas[J].Int JMol Sci,2018,19(3):33-42.
19.Kotowski U,Kadletz L,Schneider S,et al.ELMO3-a negative prognostic marker in minor salivary gland carcinoma[J].Pathol Oncol Res,2018,[Epub ahead of print].
20.Hu Y,Yu Q,Zhong Y,et al.Silencing ELMO3 Inhibits the growth,invasion,and metastasis of gastric cancer[J].Biomed Res Int,2018,2018:3764032.
21.Peng HY,Yu QF,Shen W,et al.Knockdown of ELMO3 suppresses growth,invasion and metastasis of colorectal cancer[J].Int J Mol Sci,2016,17(12):2119.
22.Gaudet J.Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4[J].Science,2002,295(5556):821-825.
23.Cui H,Gao Q,Zhang L,et al.Knockdown of FOXK1 suppresses liver cancer cell viability by inhibiting glycolysis[J].Life Sci,2018,213:66-73.
24.Chen F,Xiong W,Dou K.Knockdown of FOXK1 suppresses proliferation,migration,and invasion in prostate cancer cells[J].Oncol Res,2017,25(8):1261-1267.
25.Li L,Gong M,Zhao Y,et al.FOXK1 facilitates cell proliferation through regulating the expression of p21,and promotes metastasis in ovarian cancer[J].Oncotarget,2017,8(41):70441-70451.
26.Huang X,Xiang L,Li Y,et al.Snail/FOXK1/Cyr61 signaling axis regulates the epithelial-mesenchymal transition and metastasis in colorectal cancer[J].Cell Physiol Biochem,2018,47(2):590-603.
27.Chen D,Wang K,Li X,et al.FOXK1 plays an oncogenic role in the development of esophageal cancer[J].Biochem Biophys Res Commun,2017,494(1/2):88-94.