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背景与目的:食管癌和癌前病变组织中部分分子改变可在血液中反映出来,但这些指标的灵敏度和特异性较低,临床应用受到限制。血清蛋白质质谱分析技术有助于筛选癌变密切相关蛋白。本研究通过探讨食管癌高发区人群食管正常粘膜(normal,NOR)、食管上皮基底细胞过度增生(basalcellhyperplasia,BCH)、不典型增生(dysplasia,DYS)和食管癌(esophagealcarcinomc,EC)患者的血清蛋白质质谱的变化特征,为筛选和建立早期诊断和高危人群检测的血清学指标提供理论依据。方法:采用弱阳离子结合芯片(WCX2)及表面增强激光解吸电离飞行时间质谱仪(SELDI-TOF-MS)检测EC高发区无症状普查人群130人(NOR63人、BCH40人、DYS27人)和高发区EC30人的血清蛋白质质谱进行分析。应用BiomarkerPattern软件建立决策树分类模型,经10倍交叉验证得到该分类模型进行验证,测试组病变人群的诊断率和特异性(排除率)。结果:BCH组质荷比(M/Z)为M9306.61u的一种、DYS组M/Z为M13765.90u的一种及EC组M/Z为M2942.15u和M15953.40u的两种蛋白质分别建立决策树分类模型,训练组BCH、DYS和EC的敏感性(检出率)分别为57.5%(23/40)、88.8%(24/27)和96.6%(29/30),特异性分别为96.8%(61/63)、63.4%(40/63)和92.0%(58/63);测试组BCH、DYS和EC敏感性分别为57.5%(23/40)、66.6%(18/27)和60.0%(18/30),特异性为95.2%(60/63)、71.4%(45/63)和84.1%(53/63)。结论:M/Z为M9233.09u、M13657.15u、M2918.91u和M15827.37u的4种蛋白质可能包含有可用于食管癌高发区人群筛查的血清标记物,血清蛋白质质谱检测为食管癌和癌前病变的诊断和筛查提供了新的手段。
BACKGROUND & OBJECTIVE: Some molecular changes in esophageal cancer and precancerous lesions can be reflected in the blood. However, the sensitivity and specificity of these indicators are low, and their clinical application is limited. Serum protein mass spectrometry helps to screen for cancerous closely related proteins. This study was designed to investigate the relationship between serum protein in patients with esophageal cancer (esophageal carcinomc) and normal esophageal mucosa (normal), esophageal carcinomc (EC), basal cell hyperplasia (BCH), dysplasia (DYS) Which can provide the theoretical basis for screening and establishing the serological indexes of early diagnosis and high-risk population detection. Methods: 130 patients (NOR63, BCH40, DYS27) with high risk of asymptomatic censuses in the EC area were detected by WCX2 and SELDI-TOF-MS, EC30 human serum protein mass spectrometry analysis. The BiomarkerPattern software was used to establish the decision tree classification model. The classification model was validated by 10-fold cross-validation and the diagnostic rate and specificity (exclusion rate) of the diseased population were tested. Results: The mass-to-charge ratio (M / Z) of BCH was one of M9306.61u, the MYS of DYS was M13765.90u and the two M / Z of M2 / M were M2942.15u and M15953.40u The decision tree classification models were established. The sensitivity (detection rate) of BCH, DYS and EC in training group were 57.5% (23/40), 88.8% (24/27) and 96.6% (29/30), respectively The sensitivity of BCH, DYS and EC in the test group were 57.5% (23/40) and 66.6% (18.6%) respectively. The sensitivity of the test group was 96.8% (61/63), 63.4% (40/63) and 92.0% 27) and 60.0% (18/30) with specificity of 95.2% (60/63), 71.4% (45/63) and 84.1% (53/63), respectively. Conclusion: The four proteins with M / Z of M9233.09u, M13657.15u, M2918.91u and M15827.37u may contain serum markers for screening of esophageal cancer in high incidence areas. The detection of serum protein by mass spectrometry is esophageal cancer and Diagnosis and screening of precancerous lesions provides a new means.