子宫内膜癌组织中DAPK3和c-Myc的表达及其与患者预后的关系
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摘要
目的探讨子宫内膜癌组织中DAPK3和c-Myc的表达情况、相互关系及其对患者预后的影响。方法运用免疫组织化学SP法检测132例子宫内膜癌组织中DAPK3和c-Myc的表达,分析DAPK3、c-Myc蛋白的表达与子宫内膜癌临床病理参数的关系及对子宫内膜癌预后的影响。结果(1)132例组织标本中DAPK3低表达80例(80/132,60.61%),c-Myc高表达71例(71/132,53.79%);(2)DAPK3的表达在子宫内膜癌不同FIGO分级(P=0.034),组织学分级(P=0.027),淋巴结转移状态(P=0.022)和肌层浸润程度(P=0.011)中差异显著;c-Myc的表达在子宫内膜癌不同FIGO分级(P=0.015)和淋巴结转移状态(P=0.031)中差异显著;(3)生存曲线分析显示,DAPK3低表达患者的生存时间少于高表达患者(P=0.023),而c-Myc高表达患者的生存时间少于低表达患者(P=0.002);(4)等级相关分析显示DAPK3和c-Myc在子宫内膜癌中的表达显著负相关(r=-0.310,P<0.001);(5)COX回归分析提示,c-Myc高表达是子宫内膜癌患者预后的独立影响因素(P=0.007)。结论 DAPK3低表达和c-Myc高表达与子宫内膜癌的生长浸润行为相关,且与患者预后密切相关。通过检测DAPK3和c-Myc的表达能够更加有效地评估子宫内膜癌患者的预后。
Objective To investigate the expressions of DAPK3 and c-Myc and their prognostic value in endometrial carcinoma(EC). Methods The expressions of DAPK3 and c- Myc were detected immunohistochemically in 132 surgical specimens. The relationship between DAPK3 and c-Myc protein expressions and the clinicopathological features of the patients was evaluated.Results Immunohistochemical analysis revealed low DAPK3 expression in 60.61%(80/132) and high c- Myc expression in53.79%(71/132) of the specimens of EC. Both DAPK3 expression and c-Myc expression were significantly correlated with FIGO stage(P=0.034 and 0.015, respectively) and lymph node metastasis(P=0.022 and 0.031, respectively). DAPK3 expression was closely correlated with the histological grade(P=0.027) and depth of myometrial invasion(P=0.011). Kaplan- Meier survival analysis indicated that patients with low DAPK3 expressions had a shorter overall survival rate than those with high DAPK3expressions(P=0.023), while patients with high c- Myc expressions had poorer prognoses than those with low c- Myc expressions(P=0.002). Spearman correlation analysis showed that DAPK3 and c- Myc expressions were negatively correlated(P<0.001, r=-0.310). Multivariate analysis identified a high c-Myc expression as the independent predictor of the prognosis of EC(P=0.007). Conclusions A low expression of DAPK3 and a high expression of c- Myc are associated with aggressive and metastatic behaviors of EC, and their detection may help to predict the prognosis of the EC patients.
Objective To investigate the expressions of DAPK3 and c-Myc and their prognostic value in endometrial carcinoma(EC). Methods The expressions of DAPK3 and c- Myc were detected immunohistochemically in 132 surgical specimens. The relationship between DAPK3 and c-Myc protein expressions and the clinicopathological features of the patients was evaluated.Results Immunohistochemical analysis revealed low DAPK3 expression in 60.61%(80/132) and high c- Myc expression in53.79%(71/132) of the specimens of EC. Both DAPK3 expression and c-Myc expression were significantly correlated with FIGO stage(P=0.034 and 0.015, respectively) and lymph node metastasis(P=0.022 and 0.031, respectively). DAPK3 expression was closely correlated with the histological grade(P=0.027) and depth of myometrial invasion(P=0.011). Kaplan- Meier survival analysis indicated that patients with low DAPK3 expressions had a shorter overall survival rate than those with high DAPK3expressions(P=0.023), while patients with high c- Myc expressions had poorer prognoses than those with low c- Myc expressions(P=0.002). Spearman correlation analysis showed that DAPK3 and c- Myc expressions were negatively correlated(P<0.001, r=-0.310). Multivariate analysis identified a high c-Myc expression as the independent predictor of the prognosis of EC(P=0.007). Conclusions A low expression of DAPK3 and a high expression of c- Myc are associated with aggressive and metastatic behaviors of EC, and their detection may help to predict the prognosis of the EC patients.
引文
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[20]Wu X,Cai ZD,Lou LM,et al.Expressions of p53,c-MYC,BCL-2and apoptotic index in human osteosarcoma and their correlations with prognosis of patients[J].Cancer Epidemiol,2012,36(2):212-6.
[21]Xu AG,Li SG,Liu JH,et al.Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer[J].World J Gastroenterol,2001,7(3):403-6.
[22]Das TP,Suman S,Papu John AM,et al.Activation of AKT negatively regulates the pro-apoptotic function of death-associated protein kinase 3(DAPK3)in prostate cancer[J].Cancer Lett,2016:028.
[23]Puto LA,Brognard J,Hunter T.Transcriptional repressor DAXX promotes prostate cancer tumorigenicity via suppression of autophagy[J].J Biol Chem,2015,290(25):15406-20.
[24]吴晓云,张甦,陈爱琴,等.子宫内膜癌中基质金属蛋白酶及其组织抑制因子的表达与临床意义[J].实用妇产科杂志,2004,20(1):22-4.
[2]Matias Guiu X,Prat J.Molecular pathology of endometrial carcinoma[J].Histopathology,2013,62(1):111-23.
[3]Baser E,Gungor T,Togrul C,et al.Preoperative prediction of poor prognostic parameters and adjuvant treatment in women with pure endometrioid type endometrial cancer:what is the significance of tumor markers?[J].Eur J Gynaecol Oncol,2014,35(5):513-8.
[4]Patsner B,Yim GW.Predictive value of preoperative serum CA-125levels in patients with uterine cancer:The Asian experience 2000 to2012[J].Obstet gynecol sci,2013,56(5):281-8.
[5]Shu Ming H,Fuqi X,Hong S,et al.Determination of CA-125 levels in the serum,cervical and vaginal secretions,and endometrium in Chinese women with precancerous disease or endometrial cancer[J].Med Sci Monitor Inte Med J Exper Clin Res,2011,17(11):R618.
[6]Usui T,Okada M,Yamawaki H.Zipper interacting protein kinase(ZIPK):function and signaling[J].Apoptosis,2014,19(2):387-91.
[7]Bi J,Lau SH,Hu L,et al.Downregulation of ZIP kinase is associated with tumor invasion,metastasis and poor prognosis in gastric cancer[J].Int J Cancer,2009,124(7):1587-93.
[8]Mallipeddi R,Wessagowit V,South AP,et al.Reduced expression of insulin-like growth factor-binding protein-3(IGFBP-3)in Squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa[J].J Invest Dermatol,2004,122(5):1302-9.
[9]Bai MK,Costopoulos JS,Christoforidou BP,et al.Immunohistochemical detection of the c-myc oncogene product in normal,hyperplastic and carcinomatous endometrium[J].Oncology,1994,51(4):314-9.
[10]Dang CV,Resar LM,Emison E,et al.Function of the c-Myc oncogenic transcription factor[J].Exp Cell Res,1999,253(1):63-77.
[11]Liu Z,Yang H,Luo W,et al.Loss of cytoplasmic KLF4 expression is correlated with the progression and poor prognosis of nasopharyngeal carcinoma[J].Histopathology,2013,63(3):362-70.
[12]Li X,Gao Y,Tan M,et al.Expression of HE4 in endometrial cancer and its clinical significance[J].Biomed Res Int,2015(13):437468.
[13]Brognard J,Zhang YW,Puto LA,et al.Cancer-associated loss-offunction mutations implicate DAPK3 as a tumor-suppressing kinase[J].Cancer Res,2011,71(8):3152-61.
[14]Li J,Deng Z,Wang Z,et al.Zipper-interacting protein kinase promotes epithelial-mesenchymal transition,invasion and metastasis through AKT and NF-k B signaling and is associated with metastasis and poor prognosis in gastric cancer patients[J].Oncotarget,2015,6(10):8323-38.
[15]Wen SY,Li CH,Zhang YL,et al.Rictor is an Independent prognostic factor for endometrial carcinoma[J].Int J Clin Exp Pathol,2014,7(5):2068-78.
[16]Wang L,Jiang Q,Hua S,et al.High nuclear expression of HDGF correlates with disease progression and poor prognosis in human endometrial carcinoma[J].Dis Markers,2014(1):298795.
[17]Nicolaije KH,Ezendam NM,Vos MC,et al.Follow-up practice in endometrial cancer and the association with patient and hospital characteristics:A study from the population-based PROFILES registry[Dataset][J].Gynecol Oncol,2013,129(2):324-31.
[18]Cole MD.The myc oncogene:its role in transformation and differentiation[J].Annu Rev Genet,1986,20(20):361-84.
[19]Vita M,Henriksson M.The Myc oncoprotein as a therapeutic target for human cancer[J].Semin Cancer Biol,2006,16(4):318-30.
[20]Wu X,Cai ZD,Lou LM,et al.Expressions of p53,c-MYC,BCL-2and apoptotic index in human osteosarcoma and their correlations with prognosis of patients[J].Cancer Epidemiol,2012,36(2):212-6.
[21]Xu AG,Li SG,Liu JH,et al.Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer[J].World J Gastroenterol,2001,7(3):403-6.
[22]Das TP,Suman S,Papu John AM,et al.Activation of AKT negatively regulates the pro-apoptotic function of death-associated protein kinase 3(DAPK3)in prostate cancer[J].Cancer Lett,2016:028.
[23]Puto LA,Brognard J,Hunter T.Transcriptional repressor DAXX promotes prostate cancer tumorigenicity via suppression of autophagy[J].J Biol Chem,2015,290(25):15406-20.
[24]吴晓云,张甦,陈爱琴,等.子宫内膜癌中基质金属蛋白酶及其组织抑制因子的表达与临床意义[J].实用妇产科杂志,2004,20(1):22-4.