应用SELDI技术建立下咽鳞癌放疗疗效预测模型

Application of SELDI-TOF-MS in establishing a model for predicting radiotherapy response of hypopharyngeal cancers

目的利用表面增强激光解吸电离-飞行时间-质谱技术从蛋白质组学的角度探讨下咽鳞癌的血清蛋白质组指纹图谱。方法采集58例下咽鳞癌患者血清,采用CM10芯片和PBSⅡ-C型蛋白质芯片阅读机检测,对下咽鳞癌不同组别的血清蛋白质指纹图谱进行比较,寻找潜在的相关差异蛋白,初步建立预测下咽鳞癌放疗敏感性决策分类树模型。结果颈淋巴结转移组和无颈淋巴结转移组血清各差异蛋白峰的表达强度差别均无统计学意义(P>0.05);分化较差组和分化较好组有1个血清差异蛋白的表达强度差别有统计学意义(P<0.05),但区分度并不理想;化疗敏感组和化疗不敏感组差别无统计学意义(P>0.05);放疗敏感组和放疗不敏感组比较,P≤0.05时有5个差异性表达蛋白峰,均在放疗敏感组高表达。Biomarker Pattern软件选取2个差异性蛋白峰建立的下咽鳞癌放疗敏感性分类树预测模型,灵敏度100%(13/13),特异度83.33%(10/12)。结论下咽鳞癌放疗敏感组患者血清中m/z为6115.75的蛋白较放疗不敏感组高表达(P=0.0019)。初步建立的放疗敏感性预测模型有望用于预测下咽鳞癌的放疗敏感性。

Objective To detect the serum proteomic fingerprints in patients with hypopharyngeal squamous cell carcinoma（HPSCC） by surface enhanced laser desorption/ionization time of flight mass spectrometry（SELDI-TOF-MS） protein chip array technique.Methods The serum samples were obtained from 58 HPSCC patients for protein expression analysis using SELDI-TOF Protein Chip technique and cation-exchange（CM10） protein array.All the spectra were compared and the qualified mass peaks with mass-to-charge ratios（m/z） between 1 and 70 kD were autotimatically detected.The tree analysis pattern was generated using Biomarker Patterns Software.Results The protein profiles of HPSCC serum were analyzed according to the clinical and pathological features of the patients and their treatment response.No significant difference was noted in the serum proteins between HPSCC patients with different statuses of cervical lympha node metastasis（P0.05）,and the difference between well differentiated and poorly differentiated HPSCC was only minor.No significant difference was found in the serum proteins between chemotherapy-sensitive patients and the insensitive patients（P0.05）,but 5 proteins were identified to be overexpressed in the sensitive patients（P≤0.05）.Radiotherapy-sensitive HPSCC patients were segregated from the insensitive group with a sensitivity of 86.67% and specificity of 100%.Conclusions The serum protein at the m/z value of 6115.74 is overexpressed in radiotherapy-sensitive HPSCC patients.Serum protein profiling allows the prediction of radiotherapy response in HPSCC patients,and the identified proteins may serve as candidate biomarkers for predicting the radiotherapy sensitivity of HPSCC.