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中华结直肠疾病电子杂志 ›› 2021, Vol. 10 ›› Issue (02) : 164 -171. doi: 10.3877/cma.j.issn.2095-3224.2021.02.009

所属专题: 文献

论著

癌胚抗原(CEA)在I期结肠癌中预后意义和预后模型构建:一项基于SEER数据库的回顾性研究
王海峰1, 张红柱1, 王峰2,()   
  1. 1. 102400 北京市房山区第一医院普通外科
    2. 102218 清华大学医学附属北京清华长庚医院/清华大学临床医学院胃肠外科
  • 收稿日期:2020-10-20 出版日期:2021-04-25
  • 通信作者: 王峰

Prognosis of carcinoembryonic antigen (CEA) in stage I colon cancer and develop a prediction model: a retrospective study based on the SEER database

Haifeng Wang1, Hongzhu Zhang1, Feng Wang2,()   

  1. 1. Department of General Surgery, the First Hospital of Fangshan District, Beijing 102400, China
    2. Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
  • Received:2020-10-20 Published:2021-04-25
  • Corresponding author: Feng Wang
引用本文:

王海峰, 张红柱, 王峰. 癌胚抗原(CEA)在I期结肠癌中预后意义和预后模型构建:一项基于SEER数据库的回顾性研究[J/OL]. 中华结直肠疾病电子杂志, 2021, 10(02): 164-171.

Haifeng Wang, Hongzhu Zhang, Feng Wang. Prognosis of carcinoembryonic antigen (CEA) in stage I colon cancer and develop a prediction model: a retrospective study based on the SEER database[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2021, 10(02): 164-171.

目的

探讨术前癌胚抗原(CEA)状态在I期结肠癌中预后意义和构建I期结肠癌预后模型。

方法

应用美国国家癌症研究所的监测、流行病学和结果数据库(SEER),收集2004年至2015年诊断为I期结肠腺癌患者13 690例,通过倾向性匹配评分,探索术前CEA状态在I期结肠癌中的预后意义。应用Kaplan-Meier法绘制生存曲线,Log-rank检验分析各组生存差异。应用COX比例风险模型分析影响I期结肠腺癌患者预后的因素并构建预后模型。

结果

经过倾向性匹配评分后,T1期CEA阳性的患者5年肿瘤特异性生存率显著低于T1期CEA阴性患者(88.4% vs. 99.6%,P<0.001),T2期CEA阳性的患者5年肿瘤特异性生存率低于T2期CEA阴性患者(88.7% vs. 94.5%,P<0.001)。多因素COX分析结果显示,T1期CEA阳性患者的肿瘤特异性死亡风险相对T1期CEA阴性的患者升高了129.8%(HR=2.298,95%CI:1.775~2.974,P<0.001)。根据多因素COX回归模型结果构建列线图,并根据列线图对每位患者进行评分。在建模组中,低风险组和高风险组5年肿瘤特异性生存率分别为94.8%和90.1%(χ2=70.05,P<0.001);在验证组中,低风险组和高风险组5年肿瘤特异性生存率分别为94.3%和88.4%(χ2=41.27,P<0.001)。

结论

术前CEA阳性是I期结肠癌显著不良预后因素,根据术前CEA状态、T分期、淋巴结清扫数目、性别和年龄构建的I期结肠癌预后列线图可显著区分患者预后,应对术前CEA阳性的I期患者进行术后密切随访。

Objective

To investigate the prognostic significance of preoperative CEA status in stage I colon cancer and to establish a prognostic model for stage I colon cancer.

Methods

Based on the National Cancer Institute's Surveillance, Epidemiology, and Results Database (SEER), 13 690 patients with colon adenocarcinoma from 2004 to 2015 were assessed by propensity score matching method to determine whether preoperative CEA status affect the cancer-specific survival. Kaplan-Meier method was used to draw survival curves, Log rank test was used to analyze the survival difference of each group, and Cox proportional risk model was used to analyze the prognostic factors of stage I colon adenocarcinoma and develop a prediction model.

Results

After propensity score matching, the 5-year cancer-specific survival rate of patients with T1 stage combined with CEA positive was lower than that of patients with T1 combined with CEA negative (88.4% vs. 99.6%, P<0.001), in the same way, the 5-years- cancer-specific survival rate of patients with T2 stage combined with CEA positive was lower than that of patients with T2 combined with CEA negative (88.7% vs. 94.5%, P<0.001). Multivariate analysis showed that the risk of cancer-specific death in patients with T1 combined with CEA positive presented up to 129.8% increased risk of colon cancer-specific mortality compared with stage T1N0M0 in the context of normal serum CEA (HR=2.058, 95%CI: 1.705~2.484, P<0.001). Based on the results of multivariate analysis, we developed a nomogram and each patient was rated according to the model. In the primary cohort, the 5-year cancer-specific survival rates were 94.8% and 90.1% in the low-risk and high-risk groups, respectively (χ2=70.05, P<0.001); the 5-year cancer-specific survival rates in the validation cohort were 94.3% and 88.4% in the low-risk and high-risk groups, respectively (χ2=41.27, P<0.001).

Conclusion

Preoperative positive serum CEA is a significant adverse prognostic factor for stage I colon cancer. The prognostic model according to preoperative CEA status, T stage, number of lymph nodes harvested, gender and age could significantly distinguish the prognosis and the stage I patients with positive CEA before operation should be followed up closely after operation.

表1 倾向性匹配前与倾向性匹配后CEA(+)和CEA(-)人群基线特征比较[例(%)]
变量 PSM匹配前 χ2 P PSM匹配后 χ2 P
CEA(-)(n=10 820) CEA(+)(n=1 870) CEA(-)(n=5 740) CEA(+)(n=1 870)
性别 42.31 <0.001 0.11 1

5 359(49.5) 1 558(54.3) 3 138(54.7) 1 558(54.3)

5 461(50.5) 1 312(45.7) 2 602(45.3) 1 312(45.7)
年龄(岁) 58.43 <0.001 0 0.748

≤65

3 526(32.6) 737(25.7) 1 473(25.7) 737(25.7)

>65

7 294(67.4) 2 133(74.3) 4 267(74.3) 2 133(74.3)
种族 33.63 <0.001 0.07 0.962

白人

8 913(82.4) 2 237(77.9) 4 487(78.2) 2 237(77.9)

黑人

1 016(9.4) 365(12.7) 719(12.5) 365(12.7)

其他

891(8.2) 268(9.3) 534(9.3) 268(9.3)
T分期 56.69 <0.001 0 1

T1

3 131(28.9) 628(21.9) 1 256(21.9) 628(21.9)

T2

7 689(71.1) 2 242(78.1) 4 484(78.1) 2 242(78.1)
肿瘤部位 2.40 0.121 0.167 1

右半

6 899(63.8) 1 785(62.2) 1 256(21.9) 628(21.9)

左半

3 921(36.2) 1 085(37.8) 4 484(78.1) 2242(78.1)
淋巴结总数(个) 0.92 0.337 1.99 0.158

≤12

2 781(25.7) 763(26.6) 1 464(25.5) 763(26.6)

>12

8 039(74.3) 2 107(73.4) 4276(74.5) 2107(73.4)
肿瘤大小(mm) 62.20 <0.001 0.017 0.91

≤20

3 034(28.0) 595(20.7) 1 183(20.6) 595(20.7)

>20

7 786(72.0) 2 275(79.3) 4 557(79.4) 2 275(79.3)
分化程度 3.56 0.169 9.42 0.10

I~II

9 558(88.3) 2 571(89.6) 5 051(88.0) 2 571(89.6)

III~IV

1 043(9.6) 245(8.5) 581(10.1) 245(8.5)

未知

219(2.0) 54(1.9) 108(1.9) 54(1.9)
图1 倾向性匹配前CEA状态对I期结肠癌预后影响。1A:不同T分期与CEA状态对肿瘤特异性生存的影响;1B:不同T分期与CEA状态对总生存的影响
表2 倾向性匹配前单因素和多因素分析结果
图2 倾向性匹配后CEA状态对I期结肠癌预后影响。2A:不同T分期与CEA状态对肿瘤特异性生存的影响;2B:不同T分期与CEA状态对总生存的影响
图3 I期结肠癌5年肿瘤特异性生存列线图(nomogram)
图4 列线图建模组4A和验证组4B拟合曲线;各指标在建模组4C和验证组4D中时间依赖性ROC曲线
图5 建模组(5A)和验证组(5B)中高风险组(High-risk)和低风险组(Low-risk)的肿瘤特异性生存曲线
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