IB期非小细胞肺癌Runx2、Ezrin表达与术后转移的相关性

doi:10.6040/j.issn.1671-7554.0.2014.652

摘要/Abstract

摘要： 目的探讨IB期非小细胞肺癌(NSCLC)组织中runt相关转录因子2(Runx2)与埃兹蛋白(Ezrin)表达与临床生物学行为及术后复发转移的关系。方法收集IB期NSCLC手术切除石蜡标本40例,根据术后3年内有无复发转移分为复发/转移组和对照组,每组20例。应用免疫组化方法检测石蜡组织中Runx2与Ezrin的表达,并应用Kaplan-Meier法分析其表达与IB期NSCLC患者无病生存率之间的关系。结果复发/转移组Runx2、Ezrin的阳性表达率明显高于对照组(P=0.004, P=0.011)。Runx2、Ezrin的阳性表达在低分化的IB期NSCLC组织中较中、高分化组织中高(P=0.016, P=0.009);Runx2与Ezrin的表达呈显著正相关(r=0.646,P=0.001)。Runx2阳性和阴性表达患者术后3年无病生存率分别为30.4%、76.5%,差异有统计学意义(P=0.010);Ezrin阳性和阴性表达患者术后3年无病生存率分别为31.8%、72.2%,差异有统计学意义(P=0.011)。结论 Runx2及Ezrin表达与IB期NSCLC术后复发/转移密切相关,可以作为评估 IB期NSCLC 患者预后的指标。

关键词: 肿瘤转移, 埃兹蛋白, 非小细胞肺癌, Runt相关转录因子2

Abstract: Objective To explore the expressions of runt-related transcription factor 2 (Runx2) and Ezrin gene in stage IB non-small cell lung cancer (NSCLC) and to investigate their relationship with postoperative recurrence and metastasis. Methods Forty resected IB stage NSCLC tissues were divided into the recurrence/metastasis group with postoperative recurrence (n=20) and control group without postoperative recurrence (n=20). Immunohistochemical method was used to detect the expressions of the Runx2 and Ezrin genes. The correlation between the gene expressions and disease free survival rate of patients with stage IB NSCLC were analyzed by Kaplan-Meier. Results The positive rates of Runx2 and Ezrin expressions in the recurrence/metastasis group were significantly higher than the control group (P=0.004, P=0.011). The positive expressions of Runx2 and Ezrin in the low differentiated tissues were higher than those in the moderate and high differentiated tissues (P=0.016, P=0.009). There was a positive correlation between Runx2 and Ezrin expression (r=0.646, P=0.001). The three-year disease free survival rate was lower in patients with Runx2 and Ezrin positive expressions (30.4% and 31.8%) than those with negative expressions (76.5% and 72.2%) (P=0.010, P=0.011). Conclusion Runx2 and Ezrin expressions are closely corelative to postoperative recurrence and metastasis in patients with stage IB NSCLC, and might be potential prognostic markers in stage IB NSCLC.

Key words: Runt-related transcription factor 2, Ezrin, Non-small cell lung cancer, Neoplasm metastasis

中图分类号:

R734.2

高鹏, 沈方臻, 肖文静, 修元德, 周玲玲. IB期非小细胞肺癌Runx2、Ezrin表达与术后转移的相关性[J]. 山东大学学报（医学版）, 2015, 53(1): 63-66.

GAO Peng, SHEN Fangzhen, XIAO Wenjing, XIU Yuande, ZHOU Lingling. Correlation between the expressions of Runx2 and Ezrin and postoperative metastasis in patients with stage IB non-small cell lung cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(1): 63-66.

参考文献

[1] Chen W, Zheng R, Zhang S, et al. The incidences and mortalities of major cancers in China, 2009[J]. Chin J Cancer, 2013, 260(3):106-112.
[2] Ettinger DS, Akerley W, Borghaei H, et al. Non-small cell lung cancer, version 2.2013[J]. J Natl Compr Canc Netw, 2013, 11(6):645-653.
[3] Hung JJ, Jeng WJ, Hsu WH, et al. Predictors of death, local recurrence, and distant metastasis in completely resected pathological stage-I nonsmall-cell lung cancer[J]. J Thorac Oncol, 2012, 7(7):1115-1123.
[4] Jiang W, Chen X, Xi J, et al. Selective mediastinal lymphadenectomy without intraoperative frozen section examinations for clinical stage I non-small-cell lung cancer:retrospective study of 403 cases[J]. World J Surg, 2013, 37(2):392-397.
[5] Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions[J]. J Clin Invest, 2009, 119(6):1429-1437.
[6] Sadikovic B, Thorner P, Chilton-MacNeill S, et al. Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy [J]. BMC Cancer, 2010, 10:202.
[7] Onodera Y, Miki Y, Suzuki T, et al. Runx2 in human breast carcinoma:its potential roles in cancer progression[J]. Cancer Sci, 2010, 101(12):2670-2675.
[8] Yun SJ, Yoon HY, Bae SC, et al. Transcriptional repression of RUNX2 is associated with aggressive clinicopathological outcomes, whereas nuclear location of the protein is related to metastasis in prostate cancer[J]. Prostate Cancer and Prostatic Dis, 2012, 15(4):369-373.
[9] Pratap J, Imbalzano KM, Underwood JM, et al. Ectopic runx2 expression in mammary epithelial cells disrupts formation of normal acini structure:implications for breast cancer progression[J].Cancer Res, 2009, 69(17):6807-6814.
[10] Yang J, Zhao L, Tian W, et al. Correlation of WWOX, RUNX2 and VEGFA protein expression in human osteosarcoma[J]. BMC Med Genomics, 2013, 6:56.
[11] Baniwal SK, Khalid O, Gabet Y, et al. Runx2 transcriptome of prostate cancer cells:insights into invasiveness and bone metastasis. [J]. Mol Cancer, 2010, 9:258.
[12] Li H, Zhou RJ, Zhang GQ, et al. Clinical significance of RUNX2 expression in patients with nonsmall cell lung cancer:a 5-year follow-up study[J]. Tumour Biol, 2013, 34(3):1807-1812.
[13] Hsu YL, Huang MS, Yang CJ, et al. Lung tumor-associated osteoblast-derived bone morphogenetic protein-2 increased epithelial-to-mesenchymal transition of cancer by Runx2/Snail signaling pathway[J]. J Biol Chem, 2011, 286(43):37335-37346.
[14] Pratap J, Javed A, Languino LR, et al. The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion[J]. Mol Cell Biol, 2005, 25(19):8581-8591.
[15] Selvamurugan N, Kwok S, Partridge NC. Smad3 interacts with JunB and Cbfa1/Runx2 for transforming growth factor-beta1-stimulated collagenase-3 expression in human breast cancer cells[J]. J Biol Chem, 2004, 279(26):27764-27773.
[16] Gautreau A, Poullet P, Louvard D, et al. Ezrin, a plasma membranemicrofilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway[J]. Proc Natl Acad Sci U S A, 1999, 96(13):7300-7305.
[17] Rebillard A, Jouan-Lanhouet S, Jouan E, et al. Cisplatin-induced apoptosis involves a Fas-ROCK-ezrin-dependent actin remodelling in human colon cancer cells[J]. Eur J Cancer, 2010, 46(8):1445-1455.
[18] Jin T, Jin J, Li X, et al. Prognostic implications of ezrin and phosphorylated ezrin expression in non-small cell lung cancer[J]. BMC Cancer, 2014, 14:191.
[19] Zhang XQ, Chen GP, Wu T, et al. Expression and clinical significance of ezrin in non-small cell lung cancer[J].Clin Lung Cancer, 2012, 13(3):196-204.
[20] 闵大六,沈赞,林峰,等. Runx2和Ezrin基因在骨瘤组织中的表达及其临床意义[J].中国癌症杂志, 2012, 22(9):685-689. MIN Daliu, SHEN Zan, LIN Feng, et al. Clinical signi fi cances of Runx2 and Ezrin expressions in osteosarcoma[J]. China Oncology, 2012, 22(9):685-689.

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