切换至 "中华医学电子期刊资源库"
高级检索
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:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

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
1
Chen H, Xu C, Jin Q, et al. S100 protein family in human cancer[J]. Am J Cancer Res, 2014, 4(2): 89-115.
2
Donato R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles[J]. Int J Biochem Cell Biol, 2001, 33(7): 637-668.
3
Salama I, Malone P, Mihaimeed F, et al. A review of the S100 proteins in cancer[J]. Eur J Surg Oncol, 2008, 34 (4): 357-364.
4
Leśniak W, Słomnicki ŁP, Filipek A. S100A6-new facts and features[J]. Biochem Biophys Res Commun, 2009, 390 (4): 1087-1092.
5
Hua Z, Chen J, Sun B, et al. Specific expression of osteopontin and S100A6 in hepatocellular carcinoma[J]. Surgery, 2011, 149 (6): 783-791.
6
Komatsu K, Andoh A, Ishiguro S, et al. Increased expression of S100A6 (Calcyclin), a calcium-binding protein of the S100 family, in human colorectal adenocarcinomas[J]. Clin Cancer Res, 2000, 6 (1): 172-177.
7
Nan Y, Jin F, Yang S, et al. Discovery of a set of biomarkers of human lung adenocarcinoma through cell-map proteomics and bioinformatics[J]. Med Oncol, 2010, 27(4): 1398-1406.
8
Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014[J]. CA Cancer J Clin, 2014, 64 (1): 9-29.
9
钱桂生. 为提高我国呼吸系统疾病的诊治水平而努力[J/CD]. 中华肺部疾病杂志：电子版，2012, 5(1): 1-3.
10
李羲，钱桂生. 肺癌临床的罕见表现[J/CD]. 中华肺部疾病杂志：电子版，2013, 6(1): 4-7.
11
Ettinger DS. Ten years of progress in non-small cell lung cancer[J]. J Natl Compr Canc Netw, 2012, 10 (3): 292-295.
12
Kramer BS, Berg CD, Aberle DR, et al. Lung cancer screening with low-dose helical CT: results from the National Lung Screening Trial (NLST)[J]. J Med Screen, 2011, 18(3): 109-111.
13
Sawyers CL. The cancer biomarker problem[J]. Nature, 2008, 452(7187): 548-552.
14
Brower V. Biomarker studies abound for early detection of lung cancer[J]. J Natl Cancer Inst, 2009, 101(1): 11-13.
15
Ribé A, McNutt NS. S100A6 protein expression is different in Spitz nevi and melanomas[J]. Mod Pathol, 2003, 16(5): 505-511.
16
Cross S, Hamdy F, Deloulme JC, et al. Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers[J]. Histopathology, 2005, 46(3): 256-269.
17
Luu HH, Zhou L, Haydon RC, et al. Increased expression of S100A6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma[J]. Cancer Lett, 2005, 229(1): 135-148.
18
南岩东，姜华，金发光，等. S100A6基因干扰对A549肺腺癌细胞生物学行为的影响[J]. 国际肿瘤学杂志，2016, 43(3): 161-166.
19
Filipek A. S100A6 and CacyBP/SIP-two proteins discovered in ehrlich ascites tumor cells that are potentially involved in the degradation of β-Catenin[J]. Chemotherapy, 2006, 52(1): 32-34.
20
Schneider G, Filipek A. S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function[J]. Amino Acids, 2011, 41 (4): 773-780.
21
Ning X, Sun S, Zhang K, et al. S100A6 protein negatively regulates CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation and tumor genesis[J]. PloS One, 2012, 7(1): 30185.
[1] 衣晓丽, 胡沙沙, 张彦. HER-2低表达对乳腺癌新辅助治疗疗效及预后的影响[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 340-346.
[2] 施杰, 李云涛, 高海燕. 腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助与辅助化疗的预后及影响因素分析[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 353-361.
[3] 谭巧, 苏小涵, 侯令密, 黎君彦, 邓世山. 乳腺髓样癌的诊治进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 366-368.
[4] 李越洲, 张孔玺, 李小红, 商中华. 基于生物信息学分析胃癌中PUM的预后意义[J]. 中华普通外科学文献(电子版), 2023, 17(06): 426-432.
[5] 张俊, 罗再, 段茗玉, 裘正军, 黄陈. 胃癌预后预测模型的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(06): 456-461.
[6] 马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[7] 杨倩, 李翠芳, 张婉秋. 原发性肝癌自发性破裂出血急诊TACE术后的近远期预后及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 33-36.
[8] 栗艳松, 冯会敏, 刘明超, 刘泽鹏, 姜秋霞. STIP1在三阴性乳腺癌组织中的表达及临床意义研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 52-56.
[9] 江振剑, 蒋明, 黄大莉. TK1、Ki67蛋白在分化型甲状腺癌组织中的表达及预后价值研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 623-626.
[10] 晏晴艳, 雍晓梅, 罗洪, 杜敏. 成都地区老年转移性乳腺癌的预后及生存因素研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 636-638.
[11] 鲁鑫, 许佳怡, 刘洋, 杨琴, 鞠雯雯, 徐缨龙. 早期LC术与PTCD续贯LC术治疗急性胆囊炎对患者肝功能及预后的影响比较[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 648-650.
[12] 李永胜, 孙家和, 郭书伟, 卢义康, 刘洪洲. 高龄结直肠癌患者根治术后短期并发症及其影响因素[J]. 中华临床医师杂志(电子版), 2023, 17(9): 962-967.
[13] 王军, 刘鲲鹏, 姚兰, 张华, 魏越, 索利斌, 陈骏, 苗成利, 罗成华. 腹膜后肿瘤切除术中大量输血患者的麻醉管理特点与分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 844-849.
[14] 岳瑞雪, 孔令欣, 郝鑫, 杨进强, 韩猛, 崔国忠, 王建军, 张志生, 孔凡庭, 张维, 何文博, 李现桥, 周新平, 徐东宏, 胡崇珠. 乳腺癌HER2蛋白表达水平预测新辅助治疗疗效的真实世界研究[J]. 中华临床医师杂志(电子版), 2023, 17(07): 765-770.
[15] 索利斌, 刘鲲鹏, 姚兰, 张华, 魏越, 王军, 陈骏, 苗成利, 罗成华. 原发性腹膜后副神经节瘤切除术麻醉管理的特点和分析[J]. 中华临床医师杂志(电子版), 2023, 17(07): 771-776.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号