肝癌患者血清12种肿瘤标志物的变化

目的探讨定量测定肝癌患者血清12种肿瘤标志物的临床意义。方法用蛋白芯片技术定量测定42例正常人、46例肝癌、41例肝炎和23例肝硬化患者血清12种肿瘤标志物的变化并对检测效果进行评价。结果42例正常人CA-199(KU/L)、NSE(g/L)、CEA(g/L)、CA-242(KU/L)、Ferritin(g/L)、β-HCG(g/L)、AFP(g/L)、f-PSA(g/L)、PSA(g/L)、CA-125(KU/L)、HGH(g/L)和CA-153(KU/L)的含量分别为12.42±10.62、2.22±1.43、1.28±1.20、5.72±5.73、91.17±79.43、0.64±0.34、2.96±3.93、0.13±0.11、0.61±1.40、5.46±9.65、1.61±2.40、9.83±9.51;46例肝癌患者血清12种肿瘤标志物含量依次为:35.09±39.50、2.83±4.13、2.98±8.72、8.47±23.42、157.50±129.77、0.72±0.72、87.58±63.27、0.15±0.19、0.58±1.88、56.34±102.02、3.63±4.57、15.65±51.09;41例肝炎患者其含量依次为:76.23±96.57、4.12±4.94、2.06±3.92、4.68±6.99、298.76±326.82、1.00±0.74、63.16±91.76、0.11±0.006、0.27±0.94、18.57±36.60、3.63±4.00、6.13±6.86;23例肝硬化患者其含量依次为:49.85±75.60、5.47±14.97、1.71±1.77、12.44±34.55、278.32±326.82、0.70±0.54、52.89±98.28、0.22±0.21、2.24±4.36、111.50±191.99、2.15±0.99、10.51±15.79。该蛋白芯片测定的敏感性为50.0%,特异性为64.2%,阳性预测值为37.7%,阴性预测值为74.7%。结论采用蛋白芯片技术同时测定患者血清多种肿瘤标志物,对普查肿瘤和临床疗效观察有较好应用价值。     

不同临床期别宫颈鳞癌患者血清差异蛋白质的表达

目的寻找不同临床期别宫颈鳞癌患者之间的血清差异蛋白质。方法采用表面增强激光解吸离子化飞行时间质谱仪（SELDI-TOF-MS）和弱阳离子结合芯片（CM10）,检测宫颈鳞癌患者可手术治疗组（Ⅰa期、Ⅰb期、Ⅱa期）与不能手术治疗组（Ⅱb期、Ⅲa期、Ⅲb期、Ⅳ期）的血清蛋白质、以及血清鳞状细胞癌抗原（SCCA）≥4.5ng/ml组与SCCA〈1.5ng/ml组之间有分类意义的差异蛋白质。结果相对分子质量在1002～18369范围内,共有43种蛋白质质谱峰值有显著性差异（P〈0.05）,其中质荷比（M/Z）为11523.83、11679.13、5841.076、7971.04、16109.71、15932.17的蛋白质,在宫颈癌可手术治疗组的含量显著低于不能手术治疗组（P〈0.01）。SCCA≥4.5ng/ml组与SCCA〈1.5ng/ml组之间获得相同的差异蛋白质。以单个差异蛋白质11679.13（M/Z）作为分类变量建立宫颈癌手术组与不能手术组的诊断树模型,分类正确率为93.18%（41/44）。结论宫颈癌早中期可手术治疗组与中晚期不能手术治疗组血清中存在差异蛋白质,SCCA组≥4.5ng/ml与SCCA〈1.5ng/ml组之间存在相同的差异蛋白质;以单个差异蛋白质作为分类变量建立的诊断树模型,给临床分期提供重要的参考。     

SELDI蛋白芯片技术筛选卵巢癌血清肿瘤标志物的研究

目的寻找卵巢癌患者血清中新的肿瘤标志物。方法采用表面增强激光解吸/离子化飞行时间质谱(SELDI-TOF-MS)技术,选用WXC2蛋白质芯片对53例卵巢癌及50例对照血清标本进行检测以筛选卵巢癌患者血清中差异表达蛋白质。结果在分子量0~50 000 D范围内,检测出275个差异蛋白峰。卵巢癌差异表达明显的蛋白峰6个(P<0.05),其中低表达的5个,相对分子量分别为6 432、6 879、8 554、8 682、13 726 D,高表达的1个,相对分子质量为11 450 D。早期与晚期卵巢癌比较,发现差异表达明显的蛋白峰2个,相对分子量分别为6 190、6 448 D,均在早期卵巢癌中高表达。将发现的差异蛋白峰在Swiss蛋白数据库中搜索,发现11 450 D蛋白峰与S100 Z protein相符。S100 Z protein属于S100蛋白家族,可能通过与S100 P相互作用,促进卵巢癌的发生。其它的差异峰在数据库中没有与之相匹配的蛋白,提示可能为新的蛋白质。结论SELDI-TOF-MS蛋白质芯片技术是1种快速、简单易行、用量少和高通量分析方法,能够直接检测出卵巢癌患者血清中相对特异的肿瘤标志物,其对于卵巢癌的早期诊断具有一定的临床意义。     

Discovery of serum biomarkers in astrocytoma by SELDI–TOF MS and proteinchip technology

OBJECTIVE: To discover serum biomarkers in astrocytoma patients for early detection of glioma and evaluation of prognosis. METHODS: A total of 140 serum samples were analyzed using the weak cation-exchange (WCX) chips. Among those, 73 were sera from astrocytoma patients, 56 from normal controls, and 11 from other brain tumors. For building a diagnosis model, the samples were randomly split into a training set and a test set with similar distribution of case and control samples. Proteomics profiles were obtained using a PBSII instrument and the data were analyzed with the accompanying software. RESULTS: Seven serum biomarkers were significantly deregulated in astrocytoma group comparing to the normal control group. Among them, four were up-regulated and three were down-regulated. A decision tree classification method were developed using these seven markers. A sensitivity of 84.6% and a selectivity of 84.6% were achieved to discriminate astrocytoma from normal controls. In addition, a correlation of these markers with the astrocytoma malignancy was observed. CONCLUSIONS: Proteomics approaches such as SELDI-TOF mass spectrometry could greatly facilitate the discovery of serum biomarkers in astrocytoma. The discovered biomarkers might show great potential for early detection of astrocytoma and evaluation of prognosis for those clinical suspect astrocytoma patients. However, this need warrant further study.     

多种肿瘤标记物蛋白芯片检测系统对原发性肝癌的诊断价值

目的研究多种肿瘤标记物蛋白芯片检测系统对原发性肝癌的诊断价值.方法用该检测系统测定分析76例原发性肝癌(PHC)患者,58例良性肝病患者和145例健康查体者血清中6种常见肿瘤标记物(CA199,CEA,CA242,AFP,CA125及CA153)的水平.结果 PHC组的阳性率为82.89%,显著高于良性肝病组(41.38%)和健康查体组(4.83%,P＜0.001).不同分期PHC之间联合检测阳性率存在显著性差异,以Ⅳ组阳性率最高(P=0.011),但不同病理类型之间无显著性差异(P=0.506);不同分期之间AFP血清水平存在显著性差异(P=0.035);肝细胞癌及混合癌AFP阳性率高于胆管癌(P=0.018);联合检测在提高诊断敏感性的同时(P＜0.001),特异性有所下降(P＜0.001).结论运用蛋白芯片技术联合检测多种肿瘤标记物可以提高PHC诊断的敏感性,同时对于确定其临床分期和鉴别病理类型具有一定的意义.     

Diagnostic potential of serum protein pattern in Type 2 diabetic nephropathy.

AIMS: Microalbuminuria is the earliest clinical sign of diabetic nephropathy (DN). However, the multifactorial nature of DN supports the application of combined markers as a diagnostic tool. Thus, another screening approach, such as protein profiling, is required for accurate diagnosis. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a novel method for biomarker discovery. We aimed to use SELDI and bioinformatics to define and validate a DN-specific protein pattern in serum. METHODS: SELDI was used to obtain protein or polypeptide patterns from serum samples of 65 patients with DN and 65 non-DN subjects. From signatures of protein/polypeptide mass, a decision tree model was established for diagnosing the presence of DN. We estimated the proportion of correct classifications from the model by applying it to a masked group of 22 patients with DN and 28 non-DN subjects. The weak cationic exchange (CM10) ProteinChip arrays were performed on a ProteinChip PBS IIC reader. RESULTS: The intensities of 22 detected peaks appeared up-regulated, whereas 24 peaks were down-regulated more than twofold (P < 0.01) in the DN group compared with the non-DN groups. The algorithm identified a diagnostic DN pattern of six protein/polypeptide masses. On masked assessment, prediction models based on these protein/polypeptides achieved a sensitivity of 90.9% and specificity of 89.3%. CONCLUSION: These observations suggest that DN patients have a unique cluster of molecular components in serum, which are present in their SELDI profile. Identification and characterization of these molecular components will help in the understanding of the pathogenesis of DN. The serum protein signature, combined with a tree analysis pattern, may provide a novel clinical diagnostic approach for DN.     

胰腺癌患者血清十二种肿瘤标记物的变化

目的 探讨定量测定胰腺癌患者血清12种肿瘤标志物的临床意义。方法 用蛋白芯片技术定量测定42例正常人、30例胰腺癌和16例胰腺炎患者血清12种肿瘤标志物的变化并对检测效果进行评价。结果 42例正常人血清CA19-9(KU/L)、NSE(μg/L)、CEA(μg/L)、CA242(KU/L)、Ferritin(μg/L)、β-HCG(μg/L)、AFP(μg/L)、f-PSA(μg/L)、PSA(μg/L)、CA125(KU/L)、HGH(μg/L)和CA153(KU/L)的含量分别为:12.42±10.62、2.24±1.41、1.78±1.04、5.73±5.67、91.17±78.47、0.64±0.33、2.96±3.89、0.13±0.11、0.62±1.38、5.46±9.53、1.63±2.37、9.83±9.40;30例胰腺癌患者血清12种肿瘤标志物含量依次为:279.47±402.0、9.50±11.30、8.57±21.95、98.23±89.33、301.98±216.63、1.49±2.28、5.50±7.69、0.27±0.62、1,62±3.23、167.16±252.49、3.38±8.38、43.22±99.34;16例胰腺炎患者其含量依次为:53.38±86.38、12.78±28.50、1.20±0.94、22.99±51.13、343.43±308.27、3.63±11.99、5.09±3.66、0.10±1.32、0.66±0.61、98.67±212.23、1.79±1.63、4.15±2.13。该蛋白芯片测定的敏感性为70.0％,特异性为89.7％,阳性预测值为77.8％,阴性预测值为88.1％。结论 采用蛋白芯片技术同时测定患者血清中多种肿     

蛋白芯片筛选胶质瘤蛋白标志物的初步应用

目的 探索表面加强激光解吸电离-飞行时间质谱(surface-enhanced laser desorption/ionization time of flight mass spectrometry, SELDI TOF MS)蛋白芯片技术在星形细胞瘤早期诊断和预后判断中的应用. 方法 应用蛋白芯片生物系统(proteinchip biosystems, PBSⅡ)以及强阴离子交换芯片(strong anion-exchange, SAX2),对26例星形细胞瘤患者和22例正常人血清进行蛋白芯片检测,并用蛋白芯片软件包3.0进行数据处理和质谱分析. 结果 肿瘤组与对照组在质荷比(mass/charge, M/Z)为5911 Da、4948 Da、16494 Da、4521 Da和8593 Da处蛋白含量有显著差异,并且构建成的蛋白树状分析模式可以有效区分肿瘤患者,其灵敏度为88.46%(23/26),特异度达100%(22/22).此外,在不同级别的星形细胞瘤之间也存在差异表达的蛋白峰.结论 应用蛋白芯片质谱技术可以得到星形细胞瘤患者血清中特异性的蛋白质谱图,在早期诊断及预后判断中具有重要意义.     

肿瘤标志物蛋白芯片中胃肠道恶性肿瘤相关指标的筛选优化

目的:分析C12多肿瘤标志物蛋白芯片指标与胃肠道恶性肿瘤的相关性,筛选相关指标,为建立胃肠道恶性肿瘤小型诊断芯片提供依据。方法:使用C12多肿瘤标志物蛋白芯片系统,检测156例胃癌患者与173例结直肠癌患者术前血清中12种常见肿瘤标志物(CA19-9、NSE、CEA、CA242、CA125、CA15-3、AFP、FER、free-PSA、PSA、β-HCG及HGH)的水平,筛选出胃肠道恶性肿瘤相关指标,采用Kappa检验比较其与C12检测结果的一致性,并用成本-效果分析方法,寻找最佳组合。结果:329例胃肠道恶性肿瘤患者肿瘤标志物升高主要集中在4项指标:CEA(27.4%)、CA242(19.8%)、CA19-9(19.5%)、CA125(8.5%);使用Kappa检验比较4项指标不同组合与C12的检测结果,得出一致性极强的小型组合有6种,使用成本-效果分析法得出最佳组合为CA19-9+CEA。结论:C12多肿瘤标志物蛋白芯片系统对胃肠道恶性肿瘤的辅助诊断有一定的临床价值,但芯片设计复杂、成本较高,不利于普遍开展高危人群筛查,难以及时、实时监测病人的病情变化。因此,有必要在该芯片基础上,筛选胃肠道恶性肿瘤相关指标,设计小型芯片,在不降低检出率的情况下,增强其实际临床应用价值。     

表面增强激光解吸/离子化蛋白质芯片技术在肝细胞癌早期诊断研究中的应用

随着蛋白质组学研究技术的飞速发展,集样品分离、纯化、检测和数据分析为一体的表面增强激光解吸离子化飞行时间质谱蛋白质芯片技术已成为蛋白质组学研究的有力工具,它可以快速、简便地直接检测各种体液及分泌物,具有标本用量少、高通量分析等特点,并在筛选、鉴定肿瘤标志物及临床疾病的诊断、防治方面发挥了重要作用。本文介绍了该技术的特点和分析步骤,以及该技术在肝细胞癌早期诊断中的应用情况,并对其前景进行展望。