血清蛋白质指纹图谱对晚期结直肠癌一线化疗效果的预测作用

doi:10.3877/cma.j.issn.2095-3224.2013.02.05

目的

寻找能预测晚期结直肠癌一线化疗疗效的血清蛋白标记物。

方法

选择2008年8月至2010年7月在浙江大学医学院附属第二医院的70例从未接受过治疗的晚期结直肠癌患者，其中44例患者接受FOLFOX方案化疗，26例患者接受FOLFIRI方案化疗，进行4个疗程治疗后使用RECIST评价标准区分化疗受益者(R)和化疗无效者(NR)。留取化疗前患者血清标本，采用SELDI-TOF-MS和人工神经网络对一线化疗的疗效进行预测分析。

结果

根据RECIST标准，42例患者为化疗受益者，28例患者为化疗无效者，分析两组患者血清蛋白质指纹图谱的差异，筛选出10个蛋白质峰在化疗受益组的表达明显高于化疗无效组；并由这10个峰构建出结直肠癌一线化疗疗效的预测模型。经交叉验证，该模型的总准确率为90.0%(63/70)。

结论

蛋白质指纹图谱模型是预测晚期结直肠癌患者一线化疗方案治疗效果的有效方法之一。

关键词: 生物学标记, 结直肠肿瘤, 蛋白质阵列分析

Objective

To identify serum protein patterns which could predict the efficacy of first-line chemotherapy of metastatic colorectal cancer(CRC).

Methods

Serum from 70 patients diagnosed as metastatic colorectal cancer before first-line chemotherapy were collected and analyzed for protein patterns using ANN analysis of SELDI-TOF-MS.Among the 70 cases, 44 patients received FOLFOX regimen, while the other 26 patients received FOLFIRI regimen.After four cycles of the treatment, RECIST criteria were used to define the responders(R)and non-responders(NR).

Results

With the method of SELDI-TOF-MS, 10 protein peaks were identified to be significantly high expressed in 42 responders than in those 28 non-responders.A prediction model was constructed by the combination of these 10 peaks, which could achieve an accuracy of 90.0%(63/70)for the chemotherapy efficiency of CRC patients.

Conclusions

The prediction model combined of 10 protein peaks could be helpful for prediction of the first-line chemotherapy efficiency of metastatic CRC patients.

Key words: Biological markers, Colorectal neoplasms, Protein array analysis

表1 晚期结直肠癌患者化疗受益者(42例)与无效者(28例)蛋白质峰的比较

疗效	例数	蛋白质峰(m/z)
疗效	例数	9268	9431	9375	9298
化疗受益者(±s)	42	548.03±502.56	337.07±357.99	356.98±362.37	586.6364±552.74
化疗无效者(±s)	28	285.67±539.61	175.51±246.79	188.60±271.01	319.779±549.16
P值	?	0.000171	0.000217	0.000315	0.000396
蛋白质峰(m/z)
4304	9352	9404	4606	9198	3963
1584.676±827.35	343.3679±360.18	388.40±465.05	333.09±603.85	1602.84±2232.48	702.11±441.07
947.1406±506.90	174.2481±244.07	213.93±378.27	175.56±389.99	710.29±1786.30	500.28±305.92
0.000707	0.000707	0.000806	0.001234	0.002673	0.044639

表1 晚期结直肠癌患者化疗受益者(42例)与无效者(28例)蛋白质峰的比较

疗效	例数	蛋白质峰(m/z)
疗效	例数	9268	9431	9375	9298
化疗受益者(±s)	42	548.03±502.56	337.07±357.99	356.98±362.37	586.6364±552.74
化疗无效者(±s)	28	285.67±539.61	175.51±246.79	188.60±271.01	319.779±549.16
P值	?	0.000171	0.000217	0.000315	0.000396
蛋白质峰(m/z)
4304	9352	9404	4606	9198	3963
1584.676±827.35	343.3679±360.18	388.40±465.05	333.09±603.85	1602.84±2232.48	702.11±441.07
947.1406±506.90	174.2481±244.07	213.93±378.27	175.56±389.99	710.29±1786.30	500.28±305.92
0.000707	0.000707	0.000806	0.001234	0.002673	0.044639

表2 结直肠癌患者化疗疗效与预测模型的交叉验证结果

疗效	总例数	预测受益		预测无效
疗效	总例数	例数	百分率(%)	例数	百分率(%)
?	?	?	?	?	?
受益	42	39	91	3	11
无效	28	4	9	24	89
合计	70	43	?	27	?

表2 结直肠癌患者化疗疗效与预测模型的交叉验证结果

疗效	总例数	预测受益		预测无效
疗效	总例数	例数	百分率(%)	例数	百分率(%)
?	?	?	?	?	?
受益	42	39	91	3	11
无效	28	4	9	24	89
合计	70	43	?	27	?

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Research on the biomarkers for the prediction of efficacy in first-line chemotherapy of metastatic colorectal cancer using SELDI-TOF-MS

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Research on the biomarkers for the prediction of efficacy in first-line chemotherapy of metastatic colorectal cancer using SELDI-TOF-MS