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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2009, Vol. 03 ›› Issue (02) : 173 -180. doi: 10.3877/cma.j.issn.1674-0807.2009.02.007

实验研究

乳腺癌组织中驱动蛋白家族成员1B mRNA水平预测患者预后的临床价值
李林1, 李晓青1, 潘秀华1, 冯玉梅1,†()   
  1. 1.300060天津,天津医科大学附属肿瘤医院肿瘤研究所生物化学及分子生物学室乳腺癌防治研究教育部重点实验室
  • 收稿日期:2008-12-22 出版日期:2009-04-01
  • 通信作者: 冯玉梅
  • 基金资助:
    天津市应用基础研究项目(06YFJMJC12900)教育部长江学者和创新团队发展计划(IRT0743)

Prognostic prediction by detection of KIF1B mRNA level in breast cancer and its clinical significance

Lin LI1, Xiao-qing LI1, Xiu-hua PAN1, Yu-mei FENG†,1()   

  1. 1.Department of Biochemistry and Molecular Biology,Breast Cancer Prevention and Treatment Key Laboratory of Ministry of Education,Tianjin Medical U-niversity,Cancer Institute and Hospital,Tianjin 300060,China
  • Received:2008-12-22 Published:2009-04-01
  • Corresponding author: Yu-mei FENG
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李林, 李晓青, 潘秀华, 冯玉梅. 乳腺癌组织中驱动蛋白家族成员1B mRNA水平预测患者预后的临床价值[J/OL]. 中华乳腺病杂志(电子版), 2009, 03(02): 173-180.

Lin LI, Xiao-qing LI, Xiu-hua PAN, Yu-mei FENG. Prognostic prediction by detection of KIF1B mRNA level in breast cancer and its clinical significance[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2009, 03(02): 173-180.

目的

探讨乳腺原发癌组织中驱动蛋白家族成员1B(KIF1B)基因m RNA 表达与乳腺癌临床病理因素的关系,评估其对预测患者预后的临床价值。

方法

采用实时定量RT-PCR 方法检测180例乳腺浸润性导管癌原发癌组织中KIF1B mRNA 水平;采用受试者工作特征(ROC)曲线确定KIF1B mRNA 水平分组的阈值;χ2检验比较组间差异;Kaplan-Meier法绘制生存曲线;Log-rank 时序检验比较组间生存期的差异;多因素Cox回归模型评估KIF1B m RNA 水平对患者预后的预测价值。

结果

KIF1B mRNA 水平在各临床病理因素亚组间的差异无统计学意义;KIF1B m RNA 低水平组患者5年无病生存率和5年无转移生存率显著低于高水平组(χ2=4.714 P=0.030,χ2=4.393 P=0.036),而3年无病生存率和3年无转移生存率差异无统计学意义;KIF1B 基因表达状态、临床分期、组织学分级和PR 状态是患者独立预后因素,KIF1B mRNA 低水平组与高水平组患者发生远处转移的风险比为3.53(95%CI为1.54～8.08,P=0.003)。

结论

KIF1B m RNA 在乳腺原发癌组织中下调与患者的预后差相关,且是独立预后预测分子标志物。

关键词: 乳腺肿瘤, 驱动蛋白家族成员1B, 定量逆转录聚合酶链反应

Objective

To clarify the correlation between the m RNA level of 1B(KIF1B),one member of the kinesin family,and clinicopathologic factors in breast cancer,and to evaluate its clinical value in predicting the prognosis of breast cancer patients.

Methods

Real-time reverse transcription-polymerase chain reaction (RT-PCR)was used to detect the mRNA expression level of KIF1B in primary invasive ductal carcinoma in 180 cases.Receiver Operating Characteristic(ROC)curve was used to identify the cut-off value of KIF1B mRNA level to group the patients.Chi-square test was used to compare the differences between/among groups.Survival analysis was carried out according to Kaplan-Meier analysis.Log-rank test was used to compare the differences of survival between groups.Multivariate Cox proportional hazards regression model was used to evaluate KIF1B mRNA level for predicting the prognosis of breast cancer patients.

Results

No significant differences in KIF1B m RNA levels were found between/among groups with different clinicopathologic status.Five-year disease-free survival and metastasis-free survival of patients with low KIF1B were significantly lower than those with high KIF1B(χ2=4.714,P=0.030;χ2=4.393,P=0.036),while three-year disease-free survival and metastasis-free survival between these two groups were not found significantly different.The KIF1B status,clinical stage,histological grade,PR status were independent prognostic factors of breast cancer by analysis of Multivariate Cox proportional hazards regression model.Patients with low KIF1B had higher risk of distant metastasis than patients with high KIF1B(hazard ratio=3.53,95%CI=1.54-8.08,P=0.003).

Conclusion

The under-expressed KIF1B mRNA is correlated with poor prognosis in breast cancer patients,and is an independent molecular marker for predicting prognosis of breast cancer patients.

Key words: Breast neoplasmas, KIF1B, Quantitative RT-PCR
表1 乳腺原发癌组织中KIF1B m RNA水平与临床病理因素的关系
临床病理因素 例数 KIF1BmRNA水平 χ2值 P值
高表达例数 高表达率(%)
年龄 0.488 0.485
≤50岁 92 58 63.0
＞50岁 88 51 58.0
肿瘤大小 3.691 0.158
≤2cm 24 17 70.8
2～5cm 136 77 56.6
＞5cm 20 15 75.0
临床分期 1.414 0.234
I～II 147 86 58.5
III 33 23 69.7
组织学分级 1.522 0.467
I 3 1 33.3
II 111 71 64.0
III 23 13 56.5
缺失 43
淋巴结状态 0.845 0.358
- 76 49 64.5
+ 104 60 57.7
阳性淋巴结数 1.046 0.593
0枚 76 49 64.5
1～3枚 71 42 59.2
≥4枚 33 18 54.5
ER 1.841 0.175
+ 109 62 56.9
- 67 45 67.2
缺失 4
PR 3.076 0.079
+ 85 46 54.1
- 91 61 67.0
缺失 4
HER-2 1.501 0.221
- 70 38 54.3
+ 36 24 66.7
缺失 74
图1 KIF1B m RNA 高水平组与低水平组患者的无病生存曲线 P=0.021,两组间比较
图2 KIF1B m RNA 高水平组与低水平组患者的无转移生存曲线 P=0.023,两组间比较
表2 乳腺原发癌组织中KIF1B m RNA 水平与患者预后的关系
组别 例数 无病生存 χ2值 P值 无转移生存 χ2值 P值
例数 生存率(%) 例数 生存率(%)
随访时间3年 1.254 0.263 1.007 0.316
KIF1B高水平组 109 93 85.3 95 87.2
KIF1B低水平组 71 56 78.9 58 81.7
随访时间5年 4.714 0.030 4.393 0.036
KIF1B高水平组 78 60 76.9 62 79.5
KIF1B低水平组 54 32 59.3 34 63.0
表3 乳腺癌患者的独立预后因素
独立预后因素 回归系数(β) 标准误(Sxˉ) Wald P值 相对危险度 95%可信区间
下限 上限
KIF1B 1.262 0.422 8.925 0.003 3.532 1.543 8.082
临床分期 1.555 0.421 13.639 0.000 4.735 2.074 10.806
组织学分级 0.925 0.404 5.245 0.022 2.521 1.143 5.564
PR 1.145 0.476 5.779 0.016 3.142 1.235 7.989
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