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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) ›› 2017, Vol. 10 ›› Issue (01) : 15 -19. doi: 10.3877/cma.j.issn.1674-6902.2017.01.004

所属专题： 文献；

论著

基于免疫组化法分析肺腺癌S100A6蛋白表达与临床特征的关系
南岩东1, 房延凤1, 姜华1, 金发光1,†(), 杨拴盈2   
  1. 1. 710038　西安，第四军医大学唐都医院呼吸内科
    2. 710004　西安，西安交通大学第二附属医院呼吸内科
  • 收稿日期:2015-12-24 出版日期:2017-02-25
  • 通信作者: 金发光
  • 基金资助:
    国家自然科学基金资助项目(81001040); 第四军医大学优秀文职人员基金(2011-01); 第四军医大学唐都医院后备人才基金(5033)

Analysis of S100A6 protein expression and the clinical significance of patients with lung adenocarcinoma based on the method of immunohistochemisty

Yandong Nan1, Yanfeng Fang1, Hua Jiang1, Faguang Jin1,†(), Shuangying Yang2   

  1. 1. Department of Respiratory Disease, Tangdu Hospital, Fourth Military Medical University, Xi′an710038, China
    2. Department of Respiratory Medicine, Second Affiliated Hospital of Medical School, Xi′an Jiaotong University, Xi′an 710004, China
  • Received:2015-12-24 Published:2017-02-25
  • Corresponding author: Faguang Jin
  • About author:
    Corresponding author: Jin Faguang, Email:
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南岩东, 房延凤, 姜华, 金发光, 杨拴盈. 基于免疫组化法分析肺腺癌S100A6蛋白表达与临床特征的关系[J]. 中华肺部疾病杂志(电子版), 2017, 10(01): 15-19.

Yandong Nan, Yanfeng Fang, Hua Jiang, Faguang Jin, Shuangying Yang. Analysis of S100A6 protein expression and the clinical significance of patients with lung adenocarcinoma based on the method of immunohistochemisty[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2017, 10(01): 15-19.

目的

探讨S100A6蛋白在肺腺癌中的表达及其临床意义。

方法

收集2007年1月至2009年1月西安交通大学第二附属医院、第四军医大学唐都医院手术切除的肺癌标本，共计98例肺腺癌及其癌旁正常肺组织，用免疫组织化学法检标本中S100A6蛋白的表达情况，分析S100A6蛋白表达与患者临床病理特征及生存预后的关系。

结果

S100A6蛋白在肺腺癌组织中的表达显著高于正常肺组织(P<0.001)；其表达与患者性别和年龄无相关性(P>0.05)，而与吸烟指数、肿瘤细胞分化、淋巴结转移、远处转移、TNM分期显著相关(P<0.05)；98例患者5年随访期间77例患者死亡，10例患者存活，11例患者失访，5年生存率为11.49%。其中S100A6蛋白低表达患者5年累计生存率63.6%，中位生存时间68月；中表达患者5年累计生存率14.3%，中位生存时间45月；高表达患者5年累计生存率0%，中位生存时间29月，生存曲线显示S100A6不同表达状态患者生存率比较差异有统计学意义(P<0.05)；COX回归模型分析显示，肿瘤分化、TNM分期和S100A6表达状态是影响肺腺癌患者预后的独立因素(P<0.05)；S100A6蛋白表达对肺腺癌诊断灵敏度为84.69%，特异度为69.39%。

结论

S100A6蛋白在肺腺癌组织中显著过表达，与肿瘤分期、分化、转移及预后密切相关。

关键词: S100A6蛋白, 肺腺癌, 免疫组织化学, 预后
Objective

To explore S100A6 protein expression in lung adenocarcinoma and its clinical significance.

Methods

Immunohistochemisty (IHC) method was used to detect S100A6 protein expression in 98 cases of lung adenocarcinoma tissues and their paired adjacent normal lung tissues. The interrelation of S100A6 protein expression and clinical and pathological characteristics was analyzed by statistics methods.

Results

The expression of S100A6 protein was higher in lung adenocarcinoma tissue than that in normal lung tissue (P<0.001). The expression of S100A6 protein was not related to age and sex(P>0.05), while is significantly related to smoking index, tumor differentiation, lymph node metastasis, distant metastasis and TNM stage(P<0.05). During the 5-year follow-up period, 77 patients of 98 patients died, 10 patients survived, 11 patients were lost, and the 5-year survival rate was 11.49%. The 5-year cumulative survival rate and the median survival time are respectively 63.6% and 68 months in the patients with low expression of S100A6 protein; 14.3% and 45 months in the patients with moderate expression of S100A6 protein and 0% and 29 months in the patients with high expression of S100A6 protein. Survival curve showed that the survival rate of patients with different S100A6 expression was statistically significant (P<0.05). Cox regression model revealed that the tumor differentiation, TNM stage and S100A6 protein expression were independent hazard factors of lung adenocarcinoma prognosis (P<0.05). The diagnostic sensitivity of the S100A6 protein expression level to lung adenocarcinoma was 84.69% and the specificity was 69.39%.

Conclusions

S100A6 protein is over-expressed in lung adenocarcinoma tissue and is closely related to the differentiation, stage, metastasis and prognosis of lung adenocarcinoma.

Key words: S100A6 protein, Lung Adenocarcinoma, Immunohistochemisty, Prognosis
图1 S100A6蛋白在肺腺癌及其配对正常肺组织中表达；注：A：正常肺组织低表达；B：肺腺癌组织低表达(×10)；C：肺腺癌组织中表达；D：肺腺癌组织高表达(×40)
表1 S100A6在肺腺癌组织及正常肺组织的差异表达(%)
组　别 例数 S100A6表达
＋ ＋＋ ＋＋＋ χ2值 P值
正常肺组织 98 68(69.4) 23(23.5) 7(7.1) 12.862 <0.05
肺癌组织 98 15(15.3) 26(26.5) 57(58.2) ? ?
表2 S100A6蛋白表达与肺腺癌患者临床病理特征关系[n(%)]
临床资料 变量 例数 (＋) (＋＋) (＋＋＋) χ2值 P值
性别 男 56 9(16.1) 17(30.4) 30(53.6) 1.245 >0.05
? 女 42 6(14.3) 9(21.4) 27(64.3) ? ?
年龄 <60 57 11(19.3) 16(28.1) 30(52.6) 2.257 >0.05
? ≥60 41 4(9.8) 10(24.4) 27(65.9) ? ?
吸烟指数 NO 27 11(40.7) 9(33.3) 7(25.9) 25.009 <0.05
? <20 45 4(8.9) 12(26.7) 29(64.4) ? ?
? ≥20 26 0(0) 5(18.2) 21(80.8) ? ?
肿瘤分化 低 51 6(11.8) 11(21.6) 34(66.7) 12.32 <0.05
? 中 29 3(10.3) 7(24.1) 19(65.5) ? ?
? 高 18 6(33.3) 8(44.4) 4(22.2) ? ?
淋巴结转移 有 67 3(4.5) 14(20.9) 50(74.6) 28.632 <0.05
? 无 31 12(38.7) 12(38.7) 7(22.6) ? ?
远处转移 有 38 2(5.3) 1(2.6) 35(92.1) 29.746 <0.05
? 无 60 13(21.7) 25(41.7) 22(36.7) ? ?
临床分期 Ⅰ-Ⅱ 34 12(35.3) 14(41.2) 8(23.5) 41.601 <0.05
? Ⅲ 26 1(3.8) 11(42.3) 14(53.8) ? ?
? Ⅳ 38 2(5.3) 2(2.6) 35(92.1) ? ?
图2 S100A6不同表达状态患者生存率比较；注：A：生存函数曲线；B：危险函数曲线
表3 S100A6不同表达状态患者平均生存期比较
S100A6表达 例数 中位生存时间(月) 95%可信区间 χ2值 P值
低表达 11 68 65.72～84.46 ? ?
中表达 21 45 42.24～53.67 66.99 0.000
高表达 55 29 24.91～30.11 ? ?
图3 基于随访患者的生存；注：(A)和死亡(B)函数曲线
表4 87例肺腺癌患者生存预后的COX回归多因素分析
组　别 变　量 B SE Wald df Sig. Exp(B) 95.0% CI for Exp(B)
Lower Upper
Step 1 分期 1.613 0.207 60.686 1 0.000 5.017 3.344 7.528
Step 2 分期 1.129 0.210 28.903 1 0.000 3.093 2.049 4.669
? S100A6表达 1.488 0.298 25.008 1 0.000 4.429 2.472 7.935
Step 3 分化 －0.638 0.182 12.350 1 0.000 0.528 0.370 0.754
? 分期 1.218 0.213 32.756 1 0.000 3.381 2.228 5.131
? S100A6表达 1.592 0.315 25.574 1 0.000 4.911 2.650 9.100
表5 S100A6蛋白表达判断肺癌及正常肺组织
S100A6蛋白 金标准
肺癌组织 正常组织 合计
中、高表达 83 30 113
低表达 15 68 83
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