切换至 "中华医学电子期刊资源库"
高级检索
中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (05) : 277 -281. doi: 10.3877/cma.j.issn.1674-0807.2017.05.005

论著

Wnt-1 诱导分泌蛋白-1 表达与乳腺癌预后的关系
欧阳倩雯1,†(), 涂剑宏1, 吴晓波1, 曹亚丽1, 刘秋明1, 胡平华1, 瞿伟1, 雷秋模1   
  1. 1.330009 南昌市第三医院乳腺科
  • 收稿日期:2016-11-30 出版日期:2017-10-01
  • 通信作者: 欧阳倩雯

Relationship between Wnt-1 induced secreted protein-1 expression and prognosis of breast cancer patients

Qianwen Ouyang1,†(), Jianhong Tu1, Xiaobo Wu1, Yali Cao1, Qiuming Liu1, Pinghua Hu1, Wei Qu1, Qiumo Lei1   

  1. 1.Department of Breast Surgery, Third Hospital of Nanchang City, Nanchang 330009, China
  • Received:2016-11-30 Published:2017-10-01
  • Corresponding author: Qianwen Ouyang
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

欧阳倩雯, 涂剑宏, 吴晓波, 曹亚丽, 刘秋明, 胡平华, 瞿伟, 雷秋模. Wnt-1 诱导分泌蛋白-1 表达与乳腺癌预后的关系[J/OL]. 中华乳腺病杂志(电子版), 2017, 11(05): 277-281.

Qianwen Ouyang, Jianhong Tu, Xiaobo Wu, Yali Cao, Qiuming Liu, Pinghua Hu, Wei Qu, Qiumo Lei. Relationship between Wnt-1 induced secreted protein-1 expression and prognosis of breast cancer patients[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2017, 11(05): 277-281.

目的

探讨Wnt-1 诱导分泌蛋白-1( WISP-1)表达与乳腺癌预后的关系。

方法

本研究选取南昌市第三医院2011 年1 ~6 月手术切除且经常规病理证实的浸润性乳腺癌标本120 例及其癌旁组织进行回顾性分析。 采用免疫组织化学EnVision 两步法检测WISP-1 蛋白在120 例乳腺癌组织及其癌旁组织中的表达,同时收集这些患者的临床特征以及随访结果,采用χ2 检验分析乳腺癌组织中WISP-1 表达与患者临床病理特征的关系,采用Kaplan-Meier 法计算患者生存率,采用Log-rank 检验比较患者生存差异,并用Cox 比例风险模型分析影响乳腺癌患者预后的因素。

结果

WISP-1 在浸润性乳腺癌中的阳性表达率(85%,102/120)明显高于癌旁组织(35%,42/120)(χ2=7.653,P=0.003)。 WISP-1表达与患者的肿瘤组织学分级(χ2=22.846,P<0.001)、淋巴结转移(χ2=11.663,P=0.001)、HER-2 表达(χ2=7.825,P=0.005)以及远处转移(χ2=35.737,P<0.001)有关。 患者随访时间为24.0 ~60.0 个月,中位随访时间为43.9 个月。 生存分析结果发现,WISP-1 表达水平是患者DFS 的预后因素(χ2 =19.354,P<0.001)。 低表达WISP-1 的患者出现复发转移的中位时间是48 个月,而高表达WISP-1 的患者出现复发转移的中位时间是40 个月。 Cox 比例风险模型分析提示,WISP-1(OR=2.129, 95%CI:1.099 ~4.124,P=0.025)、年龄(OR=4.617,95%CI:2.803 ~7.605,P<0.001)、淋巴结转移(OR=2.014,95%CI:1.209~3.355, P=0.007)是乳腺癌患者DFS 的独立预后因素。

结论

高表达WISP-1 的乳腺癌患者预后更差,WISP-1 蛋白可能是乳腺癌预后的标志物。

关键词: 乳腺肿瘤, Wnt1 蛋白质, 预后

Objective

To explore the relationship between the expression of Wnt-1 induced secreted protein-1(WISP-1) and the prognosis of breast cancer patients.

Methods

The specimens of breast cancer tissue and adjacent normal breast tissue were collected from 120 cases of invasive breast cancer in Third Hospital of Nanchang City from January to June 2011. The expression of WISP-1 in specimens was measured by immunohistochemical EnVision method. The clinicopathological characteristics and follow-up results were further analyzed. The relationship between WISP-1 expression in breast cancer tissue and clinicopathological characteristics was analyzed using χ2 test. The survival rate was calculated with Kaplan-Meier method and the survival difference was analyzed with Log-rank test. The Cox proportional hazards model was used to analyze the prognostic factors in breast cancer patients.

Results

The positive rate of WISP-1 was 85% (102/120) in invasive breast cancer tissue, significantly higher than 35% (42/120) in normal breast tissue (χ2 =7.653,P=0.003). The expression of WISP-1 was correlated with histological grade (χ2=22.846,P<0.001),lymph node metastasis(χ2=11.663,P=0.001), HER-2 expression(χ2 =7.825,P=0.005) and distant metastasis(χ2=35.737,P<0.001). The follow-up time was 24.0-60.0 months, median 43.9 months. Survival analysis showed that WISP-1 expression was the prognostic factor of DFS (χ2=19.354, P<0.001). The median time to recurrence and metastasis was 48 months in patients with low expression of WISP-1, 40 months in patients with high expression of WISP-1. Cox proportional hazards model suggested that WISP-1 expression (OR=2.129,95%CI:1.099-4.124,P=0.025), age (OR=4.617,95%CI:2.803-7.605,P<0.001) and lymph node metastasis(OR=2.014,95%CI:1.209-3.355, P=0.007) were independent prognostic factors of DFS in breast cancer patients.

Conclusion

The breast cancer patients with high expression of WISP-1 have poor prognosis and WISP-1 protein can serve as an index for the prognosis of breast cancer.

Key words: Breast neoplasms, Wnt1 protein, Prognosis
表1 Cox 比例风险模型变量赋值表
变量 变量赋值
年龄 ＞35岁=0,≤35岁=1
肿瘤大小 ＜5cm=0,≥5cm=1
ER表达 阴性=0,阳性=1
PR表达 阴性=0,阳性=1
HER-2表达 阴性=0,阳性=1
组织学分级 1~2级=0,3级=1
淋巴结转移 无转移=0,有转移=1
脉管癌栓 无癌栓=0,有癌栓=1
WISP-1表达 低表达=0,高表达=1
有无远处转移 无转移=0,有转移=1
表2 120 例乳腺癌WISP-1 表达与患者临床病理特征的关系 (例)
临床病理特征 例数 WISP-1表达 χ 2值 P值
低表达 高表达
年龄
≤35岁 33 13 20 0.146 0.703
＞35岁 87 31 56
肿瘤大小
＜2cm 22 6 16 3.614 0.164
≥2cm,＜5cm 90 37 53
≥5cm 8 1 7
组织学分级
1~2级 41 27 14 22.846 ＜0.001
3级 79 17 62
淋巴结转移
无 52 28 24 11.663 0.001
有 68 16 52
ER表达
阴性 50 16 34 0.804 0.370
阳性 70 28 42
PR表达
阴性 66 27 39 1.137 0.286
阳性 54 17 37
HER-2表达
阴性 51 26 25 7.825 0.005
阳性 69 18 51
脉管癌栓
无 55 23 32 1.160 0.281
有 65 21 44
远处转移
无 41 30 11 35.737 ＜0.001
有 79 14 65
图1 Kaplan-Meier 曲线描绘120 例乳腺癌患者的无瘤生存期
表3 120 例乳腺癌患者无瘤生存率的单变量分析结果
变量 回归系数 标准误 Wald值 P值 OR值 95%置信区间
年龄 1.762 0.250 49.716 ＜0.001 5.821 3.568~9.499
肿瘤大小 0.301 0.275 1.197 0.274 1.351 0.788~2.316
ER表达 -0.335 0.226 2.190 0.139 0.716 0.460~1.115
PR表达 -0.189 0.228 0.684 0.408 0.828 0.529~1.295
HER-2表达 0.364 0.232 2.463 0.117 1.439 0.913~2.267
组织学分级 0.788 0.269 8.590 0.003 2.198 1.298~3.723
淋巴结转移 1.057 0.250 17.947 ＜0.001 2.879 1.765~4.696
脉管癌栓 0.303 0.232 1.706 0.191 1.354 0.859~2.132
WISP-1表达 1.165 0.296 15.547 ＜0.001 3.207 1.797~5.723
表4 120 例乳腺癌患者无瘤生存率的多变量分析结果
变量 回归系数 标准误 Wald值 P值 OR值 95%置信区间
年龄 1.530 0.255 36.109 ＜0.001 4.617 2.803~7.605
组织学分级 0.094 0.306 0.095 0.758 1.099 0.603~2.002
淋巴结转移 0.700 0.260 7.231 0.007 2.014 1.209~3.355
WISP-1表达 0.755 0.337 5.012 0.025 2.129 1.099~4.124
[1]
Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer[J]. Adv Exp Med Biol,2007,608:1-22.
[2]
Yeger H,Perbal B. CCN family of proteins: critical modulators of the tumor cell microenvironment.[J]. J Cell Commun Signal,2016,10(3):229-240.
[3]
Nagai Y,Watanabe M,Ishikawa S,et al. Clinical significance of Wntinduced secreted protein-1 (WISP-1/CCN4) in esophageal squamous cell carcinoma[J]. Anticancer Res,2011,31(3):991-997.
[4]
Baker R,Kent CV, Silbermann RA,et al. Pea3 transcription factors and Wnt1-induced mouse mammary neoplasia[J]. PLoS One,2010,5(1):e8854.
[5]
Holbourn KP, Acharya KR, Perbal B. The CCN family of proteins:structure-function relationships[J]. Trends Biochem Sci,2008,33(10):461-473.
[6]
Zhang H,Luo H,Hu Z,et al. Targeting WISP1 to sensitize esophageal squamous cell carcinoma to irradiation[J]. Oncotarget,2015,6(8):6218-6234.
[7]
Gurbuz I, Chiquet-Ehrismann R. CCN4/WISP1 (WNT1 inducible signaling pathway protein 1): A focus on its role in cancer[J]. Int J Biochem Cell Biol,2015,62:142-146.
[8]
Nagai Y,Watanabe M,Ishikawa S,et al. Clinical significance of Wntinduced secreted protein-1(WISP-1/CCN4) in esophageal squamous cell carcinoma[J].Anticancer Res,2011,31(3):991-997.
[9]
Davies SR,Davies ML,Sanders A, et al. Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications[J]. Int J Oncol,2010,36(5):1129-1136.
[10]
Shao H,Cai L,Moller M,et al. Notch1-WISP-1 axis determines the regulatory role of mesenchymal stem cell-derived stromal fibroblasts in melanoma metastasis[J]. Oncotarget,2016,7(48):79 262-79 273.
[11]
胡锐,田超,孟文建,等. Wnt-1 诱导分泌蛋白-1 在乳腺浸润性导管癌中的表达及其临床意义[J]. 四川大学学报(医学版), 2010,41(2):231-234.
[12]
Banerjee S,Sengupta K, Saxena NK, et al. Epidermal growth factor induces WISP-2/CCN5 expression in estrogen receptor-alpha-positive breast tumor cells through multiple molecular cross-talks[J]. Mol Cancer Res,2005,3(3):151-162.
[13]
Kleer CG, Zhang Y, Pan Q, et al. WISP3 (CCN6) is a secreted tumor-suppressor protein that modulates IGF signaling in inflammatory breast cancer[J]. Neoplasia,2004,6(2):179-185.
[14]
Zhang Y, Pan Q, Zhong H, et al. Inhibition of CCN6 (WISP3)expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells[J]. Breast Cancer Res,2005,7(6):1080-1089.
[15]
Daves SR,Watkins G,Mansel RE, et al. Differential expression and prognostic implications of the CCN family members WISP-1, WISP-2,and WISP-3 in human breast cancer[J]. Ann Surg Oncol,2007,14(6):1909-1918.
[16]
Yang JY, Yang MW, Huo YM, et al. High expression of WISP-1 correlates with poor prognosis in pancreatic ductal adenocarcinoma[J].Am J Transl Res,2015,7(9):1621-1628.
[17]
罗宏涛,车团结,王小虎,等. 放射治疗后血清YKL-40 变化对乳腺癌患者预后判断的价值[J/CD].中华乳腺病杂志(电子版),2016,10(4):215-219.
[18]
胡保全,胡春艳,姜军,等. 转录因子Twist 在乳腺癌中的作用及研究进展[J/CD].中华乳腺病杂志(电子版),2016,10(4):239-242.
[19]
孙子涵,潘沁汶,苑龙,等. ERβ 和PTEN 在人乳腺癌组织中的表达及其临床意义[J/CD]. 中华乳腺病杂志(电子版),2016,10(5):276-281.
[1] 李洋, 蔡金玉, 党晓智, 常婉英, 巨艳, 高毅, 宋宏萍. 基于深度学习的乳腺超声应变弹性图像生成模型的应用研究[J/OL]. 中华医学超声杂志（电子版）, 2024, 21(06): 563-570.
[2] 周荷妹, 金杰, 叶建东, 夏之一, 王进进, 丁宁. 罕见成人肋骨郎格汉斯细胞组织细胞增生症被误诊为乳腺癌术后骨转移一例[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 380-383.
[3] 韩萌萌, 冯雪园, 马宁. 乳腺癌改良根治术后桡神经损伤1例[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 117-118.
[4] 许杰, 李亚俊, 韩军伟. 两种入路下腹腔镜根治性全胃切除术治疗超重胃癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 19-22.
[5] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[6] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[7] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[8] 顾雯, 凌守鑫, 唐海利, 甘雪梅. 两种不同手术入路在甲状腺乳头状癌患者开放性根治性术中的应用比较[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 687-690.
[9] 付成旺, 杨大刚, 王榕, 李福堂. 营养与炎症指标在可切除胰腺癌中的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 704-708.
[10] 关小玲, 周文营, 陈洪平. PTAAR在乙肝相关慢加急性肝衰竭患者短期预后中的预测价值[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 841-845.
[11] 张润锦, 阳盼, 林燕斯, 刘尊龙, 刘建平, 金小岩. EB病毒相关胆管癌伴多发转移一例及国内文献复习[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 865-869.
[12] 陈晓鹏, 王佳妮, 练庆海, 杨九妹. 肝细胞癌VOPP1表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 876-882.
[13] 刘郁, 段绍斌, 丁志翔, 史志涛. miR-34a-5p 在结肠癌患者的表达及其与临床特征及预后的相关性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 485-490.
[14] 陈倩倩, 袁晨, 刘基, 尹婷婷. 多层螺旋CT 参数、癌胚抗原、错配修复基因及病理指标对结直肠癌预后的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 507-511.
[15] 王景明, 王磊, 许小多, 邢文强, 张兆岩, 黄伟敏. 腰椎椎旁肌的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 846-852.
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