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中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2010, Vol. 04 ›› Issue (04) : 350 -354. doi: 10.3877/cma.j.issn.1674-0793.2010.04.014

所属专题： 文献；

论著

癌组织K-ras基因突变、术前血清CEA水平与结直肠癌临床病理特点的关系
吴文辉1, 汤友珍2, 肖隆斌1,†(), 蔡世荣3, 何裕隆3, 詹文华3   
  1. 1. 510700　广州，中山大学附属第一医院黄埔院区普外科
    2. 510700　广州，中山大学附属第一医院黄埔院区预防保健科
    3. 中山大学附属第一医院胃肠胰外科
  • 收稿日期:2010-01-05 出版日期:2010-08-01
  • 通信作者: 肖隆斌
  • 基金资助:
    广州市黄埔科技计划资助项目(2009031)

Detection of K-ras gene mutations in cancer tissues, preoperative carcinoembryonic antigen in serums of patients with colorectal cancer and their correlation with clinical pathological characteristics

Wen-hui WU1, You-zhen TANG2, Long-bin XIAO1,†(), Shi-rong CAI3, Yu-long HE3, Wen-hua ZHAN3   

  1. 1. Department of General Surgery, Huangpu Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510700, China
  • Received:2010-01-05 Published:2010-08-01
  • Corresponding author: Long-bin XIAO
  • About author:
    Corresponding author: XIAO Long-bin, Email:
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引用本文：

吴文辉, 汤友珍, 肖隆斌, 蔡世荣, 何裕隆, 詹文华. 癌组织K-ras基因突变、术前血清CEA水平与结直肠癌临床病理特点的关系[J/OL]. 中华普通外科学文献(电子版), 2010, 04(04): 350-354.

Wen-hui WU, You-zhen TANG, Long-bin XIAO, Shi-rong CAI, Yu-long HE, Wen-hua ZHAN. Detection of K-ras gene mutations in cancer tissues, preoperative carcinoembryonic antigen in serums of patients with colorectal cancer and their correlation with clinical pathological characteristics[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2010, 04(04): 350-354.

目的

观察结直肠癌组织中K-ras基因突变情况，术前检测患者血清CEA水平，探讨两者与结直肠癌临床病理的关系。

方法

应用实时荧光定量PCR方法和基因测序技术检测100例结直肠癌组织中K-ras基因12、13密码子突变情况，化学发光法检测患者血清CEA水平，结合其临床病理资料进行统计学分析。

结果

K-ras基因突变者39例（39.0%），其中12号密码子突变31例，13号密码子突变8例。有淋巴结转移者K-ras基因突变率（57.8%）明显高于无淋巴结转移者（23.6%），有肝脏转移者K-ras基因突变率（62.5%）明显高于无肝转移者（34.5%），TNM分期Ⅲ、Ⅳ期K-ras基因突变率（56.5%）明显高于Ⅰ、Ⅱ期（24.1%）。K-ras基因突变率与肿瘤大小、部位、肿瘤浸润深度、分化程度无密切关系。49例CEA水平超出正常范围（49.0%）。有淋巴结转移或肝转移患者CEA水平显著高于无淋巴结或肝转移患者（P<0.05）。在肿瘤不同的临床病理分期（Duke's、TNM分期）间CEA水平差异有统计学意义，Duke's D期和TNM Ⅲ、Ⅳ期出现高阳性率。CEA水平在肿瘤不同浸润深度、体积及分化程度上无明显差异。

结论

癌组织K-ras基因突变和血清CEA水平超出正常水平预示结直肠癌可能合并淋巴结转移或肝转移，是预后不良的指标。

关键词: 结直肠肿瘤, ras，基因, 突变, 癌胚抗原
Objective

To detect mutations of K-ras gene in cancer tissues and preoperative carcinoembryonic antigen in serums of patients with colorectal cancer, and to find out their correlation with clinical pathological characteristics of colorectal cancer.

Methods

The specimens of 100 patients with colorectal cancer were collected. Real-time fluorescence quantitative PCR and DNA sequencing were performed in these tissues to detect K-ras gene mutations at codon 12th and codon 13th, and preoperative carcinoembryonic antigen level in serums were evaluated by radioimmunoassay, the results were analyzed with patients' clinical pathological data.

Results

Thirty-nine cases (39.0%) were detected pointmutation, and 31(31.0%)cases were found pointmutation at codon 12th, eight cases(8.0%) at codon 13th. The rate of K-ras gene mutation in cases with metastatic lymph nodes(57.8%) was higher than that in cases with no metastatic lymph node(23.6%). The mutation rate in cases with liver metastasis(62.5%) was higher than that in cases without liver metastasis(34.5%), P<0.05. And significant differences were found between TNM III, IV(56.5%) and TNM I, II(24.1%). There were no closely relationship with size, location, invasive depth and differentiation extent of tumor. CEA levels in 49 patients were positive (more than 5μg/L). Patients with lymph node or liver metastasis had a high lever of CEA. The positive rate of CEA level in patients with liver/lymph node metastasis was 75% and 73.3% respectively, which was higher than that in patients without liver/lymph node metastasis(44%, 29.1%), P<0.05. Significant differences between Duke′s stages/TNM stages were found with high positive rate in the groups of Duke′s D stage and TNM III, IV stages. CEA levels had no relationship with size, location, invasive depth or differentiation extent of tumor.

Conclusion

K-ras gene mutation and CEA level are closely associated with liver and/or lymph node metastasis in colorectal cancer. They are negative prognostic factors of colorectal cancer.

Key words: Colorectal neoplasms, Ras gene, Mutation, CEA
图1 野生型K-ras基因实时荧光PCR扩增产物荧光曲线图
图2 突变型K-ras基因实时荧光PCR扩增产物荧光曲线图
表1 K-ras基因突变与临床病理特征关系（例）
病理特征 例数 K-ras CEA
突变 χ2值 P值 阳性 χ2值 P值
肿瘤直径(cm) ? ? ? ? ? ? ?
? ≤5 62 25 0.120 0.729 28 0.962 0.327
? >5 38 14 21
肿瘤部位 ? ? ? ? ? ? ?
? 右半结肠 27 9 ? ? 12 ? ?
? 左半结肠 30 11 0.919 0.632 16 0.450 0.798
? 直肠 43 19 ? ? 21 ? ?
分化程度 ? ? ? ? ? ? ?
? 高 28 10 ? ? 13 ? ?
? 中 41 17 0.233 0.890 19 0.613 0.736
? 低 31 12 ? ? 17 ? ?
肿瘤侵润深度 ? ? ? ? ? ? ?
? 局限于肠壁内 58 24 0.329 0.566 27 0.331 0.565
? 侵出肠壁 42 15 22
淋巴结转移 ? ? ? ? ? ? ?
? 无 55 13 17.907 0.000 16 19.386 0.000
? 有 45 26 33
肝转移 ? ? ? ? ? ? ?
? 有 16 10 4.422 0.035 12 5.153 0.023
? 无 84 29 37
Duke's分期 ? ? ? ? ? ? ?
? A 24 3 ? ? 6 ? ?
? B 31 10 15.603 0.001 14 11.117 0.011
? C 29 15 17
? D 16 11 ? ? 12 ? ?
TNM分期 ? ? ? ? ? ? ?
? Ⅰ、Ⅱ 54 13 10.993 0.001 16 17.626 0.000
? Ⅲ、Ⅳ 46 26 33
图3 野生型K-ras基因第12、13密码子基因序列分别为GGT、GGC
图4 K-ras基因12密码子GGT突变为GAT
图5 K-ras基因12密码子GGT突变为GTT
图6 K-ras基因13密码子GGC突变为GAC
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