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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2019, Vol. 12 ›› Issue (04) : 430 -435. doi: 10.3877/cma.j.issn.1674-6902.2019.04.006

论著

MEIS2、BRCA1表达的相关性及与术后非小细胞肺癌化疗预后的关系
黄长江1, 聂婷婷2, 王迎难2,†(), 倪吉祥2,†()   
  1. 1. 443000　宜昌，三峡大学人民医院·宜昌市第一人民医院呼吸与危重症医学科；445000　恩施，恩施州土家族苗族自治州中心医院ICU
    2. 443000　宜昌，三峡大学人民医院·宜昌市第一人民医院呼吸与危重症医学科
  • 收稿日期:2019-04-10 出版日期:2019-08-20
  • 通信作者: 王迎难, 倪吉祥
  • 基金资助:
    湖北省科技厅自然科学基金资助项目(2014CFB689)

Relationship between expression of MEIS2 and BRCA1 and prognosis of non-small-cell lung carcinoma after operation and chemotherapy

Changjiang Huang1, Tingting Nie2, Yingnan Wang2,†(), Jixiang Ni2,†()   

  1. 1. Department of respiratory and critical medicine, Yichang First People′s Hospital, China Three Gorges University people′s Hospital, 443000 Yichang, China; Department of ICU, the Central Hospital of Enshi Tujia and Miao Autonomoud prefecture, Enshi 445000, China
    2. Department of respiratory and critical medicine, Yichang First People′s Hospital, China Three Gorges University people′s Hospital, 443000 Yichang, China
  • Received:2019-04-10 Published:2019-08-20
  • Corresponding author: Yingnan Wang, Jixiang Ni
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引用本文：

黄长江, 聂婷婷, 王迎难, 倪吉祥. MEIS2、BRCA1表达的相关性及与术后非小细胞肺癌化疗预后的关系[J]. 中华肺部疾病杂志(电子版), 2019, 12(04): 430-435.

Changjiang Huang, Tingting Nie, Yingnan Wang, Jixiang Ni. Relationship between expression of MEIS2 and BRCA1 and prognosis of non-small-cell lung carcinoma after operation and chemotherapy[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2019, 12(04): 430-435.

目的

探讨非小细胞肺癌(NSCLC)中MEIS2、BRCA1基因表达的相关性及与术后NSCLC化疗预后的关系。

方法

收集宜昌市第一人民医院2012年2月至2016年1月住院手术切除并经病理确诊NSCLC的石蜡包埋组织标本61例，收集整理标本对应患者的临床资料，随访患者生存情况。应用免疫组化检测组织中MEIS2及BRCA1基因的表达，分析两者表达的相关性，并将MEIS2、BRCA1表达纳入生存分析，研究两者与NSCLC术后辅助化疗疗效之间的相关性。

结果

61例NSCLC患者中，MEIS2和BRCA1的高表达率分别为57.38%(35/61)和65.57%(40/61)，两者表达呈正相关(r＝0.59，P＝0.003)。NSCLC患者接受基于铂类药物化疗4～6周期化疗后，20例CR+PR(32.8%)，41例SD+PD(67.2%)，MEIS2低表达患者有效率为21.3% (13/61)，而MEIS2高表达有效率为11.5% (7/61)，有极显著性差异(P<0.01)；BRCA1低表达患者有效率为23.0% (14/61)，而BRCA1高表达有效率为9.8% (6/61)，有极显著性差异(P<0.01)。

结论

免疫组化显示MEIS2和BRCA1两者的表达存在显著正相关，MEIS2和BRCA1的表达与NSCLC术后接受铂类药物化疗的预后相关，MEIS2和BRCA1表达越低，化疗疗效越好。

关键词: 非小细胞肺癌, MEIS2, BRCA1基因, 免疫组织化学技术
Objective

To explore the correlation between the expression of MEIS2 and BRCA1 and the prognosis of non-small-cell lung carcinoma (NSCLC) after operation and chemotherapy.

Methods

A total of 61 paraffin-embedded tissue samples were collected from the patients with surgically-resected and pathologically-diagnosed NSCLC (non-small cell lung cancer) in Yichang First People′s Hospital from February 2012 to January 2016. The personal information, clinical information and survival follow-up data of those patients were also collected and analyzed. Immunohistochemical staining was employed to detect the expression levels of MEIS2 and BRCA1, and the correlation between the expression levels of MEIS2 and BRCA1 was analyzed and the two kinds of gene expression were brought into survival analysis. The relationship between MEIS2 and BRCA1 expression and the curative effect of postoperative adjuvant chemotherapy of NSCLC was studied, too.

Results

The patients with NSCLC were treated with platinum-based chemotherapy for 4-6 treatment cycles: effective in 20 patients, with CR+ PR=32.8%, and ineffective in 41 patients, with SD+ PD=67.2%. The effective rate of low expression of BRCA1 was 23.0% (14/61) and high expression of BRCA1 was 9.8% (6/61), and obvious significant difference was found (r=0.59, P=0.003). The effective rate of low expression of MEIS2 expression was 21.3% (13/61) and high expression of MEIS2 was 11.5% (7/61), and obvious significant difference was found (P<0.01).

Conclusion

The immunohistochemical results show that the expression levels of BRCA1 and MEIS2 are significantly positively correlated, and the expression levels of MEIS2 and BRCA1 are correlated with the prognosis of chemotherapy in the patients with NSCLC. The lower the expression levels of BRCA1 and MEIS2 are, the better the chemotherapeutic effect is.

Key words: Non-small-cell lung carcinoma, MEIS2 gene, BRCA1 gene, Immunohistochemical staining
图1 MEIS2在鳞癌及腺癌组织中的高表达(×200)
图2 BRCA1在鳞癌及腺癌组织中的高表达(×200)
表1 患者临床资料及免疫组化结果
临床资料 例数 BRCA1 MEIS2
高表达 低表达 χ2值 P值 高表达 低表达 χ2值 P值
合　计 61 40 21     35 26    
性别                  
  男 43 25 18 3.568 0.052 24 19 0.146 0.464
  女 18 15 3     11 7    
年龄                  
  >60岁 31 17 14 3.218 0.063 19 12 0.395 0.356
  ≤60岁 30 23 7     16 14    
病理分类                  
  鳞癌 26 15 11 1.247 0.199 14 12 0.066 0.501
  腺癌 35 25 10     21 14    
分期                  
  Ⅰ+Ⅱ 35 21 14 1.130 0.215 19 16 0.321 0.381
  Ⅲ+Ⅳ 26 19 7     16 10    
吸烟                  
  是 34 22 12 0.026 0.545 18 16 0.618 0.300
  否 27 18 9     17 10    
表2 MEIS2、BRCA1的表达与化疗方案
BRCA1表达 化疗方案 合计 χ2值 P值
GP DP PC
高表达 23 7 10 40 0.594 0.743
低表达 10 5 6 21    
MEIS2表达         0.416 0.812
高表达 20 6 9 35    
低表达 13 6 7 26    
合计 33 12 16 61    
图3 MEIS2基因表达与疾病进展时间的关系P＝0.000(月)
图4 BRCA1基因表达与疾病进展时间的关系P＝0.000(月)
1
Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
2
Sculier JP, Meert AP. Third-generation chemotherapy agents in the treatment of advanced non-small cell lung cancer: a meta-analysis[J]. J Thorac Oncol, 2008, 3(3): 320, 320-322.
3
Reguart N, Cardona AF, Carrasco E, et al. BRCA1: a new genomic marker for non-small-cell lung cancer[J]. Clin Lung Cancer, 2008, 9(6): 331-339.
4
黄长江，赵天明，张家祺，等. MEIS2基因沉默致A549细胞凋亡、细胞周期阻滞及调控机制研究[J]. 国际呼吸杂志，2018(12): 886-892.
5
Geerts D, Revet I, Jorritsma G, et al. MEIS homeobox genes in neuroblastoma[J]. Cancer Lett, 2005, 228(1-2): 43-50.
6
Chen JL, Li J, Kiriluk KJ, et al. Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression[J]. Clin Cancer Res, 2012, 18(16): 4291-4302.
7
Crijns AP, de Graeff P, Geerts D, et al. MEIS and PBX homeobox proteins in ovarian cancer[J]. Eur J Cancer, 2007, 43(17): 2495-2505.
8
Zha Y, Xia Y, Ding J, et al. MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progression[J]. Cell Death Dis, 2014, 5: e1417.
9
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
10
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017[J]. CA Cancer J Clin, 2017, 67(1): 7-30.
11
Kohler BA, Sherman RL, Howlader N, et al. Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State[J]. J Natl Cancer Inst, 2015, 107(6): v48.
12
Movik E, Juvet LK, Hamidi V, et al. Pemetrexed as Maintenance Therapy for Advanced, Non-Squamous, Non-Small Cell Lung Cancer (NSCLC)[M]. Oslo, Norway: Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH), 2012: 12-23.
13
石远凯，孙　燕，于金明，等. 中国晚期原发性肺癌诊治专家共识(2016年版)[J]. 中国肺癌杂志，2016, 19(1): 1-15.
14
Steger V, Walles T, Kosan B, et al. Trimodal therapy for histologically proven N2/3 non-small cell lung cancer: mid-term results and indicators for survival[J]. Ann Thorac Surg, 2009, 87(6): 1676-1683.
15
Kenzik KM, Martin MY, Fouad MN, et al. Health-related quality of life in lung cancer survivors: Latent class and latent transition analysis[J]. Cancer, 2015, 121(9): 1520-1528.
16
Xue C, Hu Z, Jiang W, et al. National survey of the medical treatment status for non-small cell lung cancer (NSCLC) in China[J]. Lung Cancer, 2012, 77(2): 371-375.
17
姚晓军，刘伦旭. 肺癌的流行病学及治疗现状[J]. 现代肿瘤医学，2014, 22(8): 1982-1986.
18
Lopez-Lazaro M. The stem cell division theory of cancer[J]. Crit Rev Oncol Hematol, 2018, 123: 95-113.
19
Yang Y, Xie Y, Xian L. Breast cancer susceptibility gene 1 (BRCA1) predict clinical outcome in platinum-and toxal-based chemotherapy in non-small-cell lung cancer (NSCLC) patients: a system review and meta-analysis[J]. J Exp Clin Cancer Res, 2013, 32: 15.
20
Tung NM, Garber JE. BRCA1/2 testing: therapeutic implications for breast cancer management[J]. Br J Cancer, 2018, 119(2): 141-152.
21
Brabec V, Kasparkova J. Molecular aspects of resistance to antitumor platinum drugs[J]. Drug Resist Updat, 2002, 5(3-4): 147-161.
22
Wang Y, Cortez D, Yazdi P, et al. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures[J]. Genes Dev, 2000, 14(8): 927-939.
23
Kang CH, Jang BG, Kim DW, et al. The prognostic significance of ERCC1, BRCA1, XRCC1, and betaⅢ-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection[J]. Lung Cancer, 2010, 68(3): 478-483.
24
Rosell R, Skrzypski M, Jassem E, et al. BRCA1: a novel prognostic factor in resected non-small-cell lung cancer[J]. PLoS One, 2007, 2(11): e1129.
25
Lewis EB. Homeosis: the first 100 years[J]. Trends Genet, 1994, 10(10): 341-343.
26
黄长江，倪吉祥，王迎难. HOX基因在肺癌中的研究进展[J]. 国际呼吸杂志，2015, 35(22): 1730-1733.
27
Knoepfler PS, Kamps MP. The pentapeptide motif of Hox proteins is required for cooperative DNA binding with Pbx1, physically contacts Pbx1, and enhances DNA binding by Pbx1[J]. Mol Cell Biol, 1995, 15(10): 5811-5819.
28
Paige SL, Thomas S, Stoick-Cooper CL, et al. A temporal chromatin signature in human embryonic stem cells identifies regulators of cardiac development[J]. Cell, 2012, 151(1): 221-232.
29
Agoston Z, Li N, Haslinger A, et al. Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development[J]. BMC Dev Biol, 2012, 12: 10.
30
Bessa J, Tavares MJ, Santos J, et al. meis1 regulates cyclin D1 and c-myc expression, and controls the proliferation of the multipotent cells in the early developing zebrafish eye[J]. Development, 2008, 135(5): 799-803.
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