结直肠癌肿瘤标志物的研究进展

结直肠癌是目前最常见消化道恶性肿瘤之一.由于这类疾病早期常无症状,往往诊断较晚,导致该疾病的死亡率一直居高不下.因此,结直肠癌的早发现、早诊断、早治疗显得尤为重要,而目前其诊断主要依赖内镜、影像学检查以及肿瘤标志物等血清学检查.其中,肿瘤标志物在结直肠癌的诊断、预后判断及检测复发等方面具有重大意义.因此,迫切需要发现可...     

质谱MRM技术在生物标志物研究中的应用

质谱多反应监测（multiple reaction monitoring,MRM）技术是一种基于已知信息或假定信息设定质谱检测规则,针对性的获取数据的方式,具有高选择性、高特异性、高灵敏度等优点,在基于蛋白质组学的生物标志物研究中,逐渐受到研究者的重视.从MRM定义、MRM在生物标志物研究中的优势、应用及其局限性和前景进行综述.     

结直肠癌患者血清肿瘤标志物联合检测的临床意义

目的探讨血清肿瘤标志物联合检测在结直肠癌(CRC)患者病情监测中的临床意义。方法 116例CRC患者根据不同肿瘤分期分为Ⅰ~Ⅱ期组50例和Ⅲ~Ⅳ期组66例,比较2组血清肿瘤标志物水平。同时比较化疗后12个月和24个月时复发转移与未复发转移者血清肿瘤标志物水平差异。结果Ⅰ~Ⅱ期组患者血清癌胚抗原(CEA)、糖链抗原19-9(CA19-9)和CA242水平均显著低于Ⅲ~Ⅳ期组,差异有统计学意义(P0.05);2组血清甲胎蛋白(AFP)、CA724水平比较,差异无统计学意义(P0.05);化疗后12个月,复发转移与无复发转移患者血清CEA、CA199、CA242、CA724水平比较,差异有统计学意义(P0.05);2组血清AFP水平比较,差异无统计学意义(P0.05);化疗后24个月,复发转移与无复发转移患者血清CEA、CA199、CA242、AFP、CA724水平比较,差异有统计学意义(P0.05)。结论血清肿瘤标志物联合检测在评估CRC患者病情、监测化疗后是否复发转移上具有一定临床价值。     

用SELDI蛋白芯片技术筛选缺血性脑卒中患者血清蛋白标志物的研究

目的研究缺血性脑卒中患者血清蛋白质谱的变化,从而筛选特异性的蛋白标志物。方法采用表面增强激光解吸离子化飞行时间质谱（SELDI-TOF-MS）技术和弱阳离子交换芯片（CM10）首先对训练组72例缺血性脑卒中患者和性别年龄匹配的80例正常对照者血清蛋白表达谱的差异进行分析,建立决策树分类模型后,对测试组（55例缺血性脑卒中患者和60例正常对照者）进行盲法验证。结果在质荷比（M/Z）2000～50000Da范围内,共检测到94个蛋白质峰,筛选出差异蛋白质峰29个,以质荷比（M/Z）分别为5659、5878、7304、7398和9003Da的5个差异蛋白峰,建立的决策树分类模型对缺血性脑卒中患者诊断的敏感性为95.8%（69/72）,特异性为97.5%（78/80）,正确诊断率为96.7%（147/152）。用该模型对测试组进行双盲检测,结果显示敏感性、特异性和正确诊断率分别为94.5%（52/55）、95.0%（57/60）和94.8%（109/115）。结论应用SELDI-TOF-MS技术可以筛选出缺血性脑卒中患者相关的血清蛋白标志物,建立的决策树分类模型可能对缺血性脑卒中患者的诊断具有重要的临床价值。     

LncRNA-CCAT2在结直肠癌患者中的表达及其临床意义

目的 探讨长链非编码RNA结肠癌相关转录物2(LncRNA-CCAT2)在结直肠癌(CRC)患者中的表达及其临床意义.方法 收集2017年1月至2017年7月汉中市中心医院治疗的40例CRC患者的癌组织、癌旁组织、血清标本及40例无瘤患者的血清标本.运用实时荧光定量PCR(RT-qPCR)方法分别检测标本中LncRNA...     

应用蛋白质芯片技术筛选阿尔茨海默病血清标志物

目的用表面加强激光解析电离飞行时间质谱（SELDI-TOF-MS）蛋白质芯片检测阿尔茨海默病（AD）患者血清蛋白质指纹图谱,探讨诊断模型在AD诊断中的临床应用价值。方法用SELDI-TOF-MS技术和CM10蛋白质芯片检测45例患者AD和60例健康老人的血清蛋白质指纹图谱,并建立诊断模型。结果筛选出11个有明显表达差异的蛋白质,其中以质荷比（m/z）分别为4604.2、7775.7和9200.6的3个蛋白质建立的诊断模型对AD检测的灵敏度为88.9%（40/45）,特异性为85.0%（51/60）,总准确率为86.67%（91/105）。结论 SELDI-TOF-MS对AD诊断具有较高的敏感性和特异性,在AD的诊断及标志物筛选等方面具有较好的诊断价值。     

应用表面增强激光解吸电离飞行时间质谱联合磁珠技术寻找肺癌血清蛋白标志物

  目的  建立肺癌蛋白质指纹图谱诊断模型, 探讨用于肺癌早期诊断及手术疗效评估的血清蛋白标志物。  方法  收集38例肺癌患者、12例肺部良性肿瘤患者及32名正常对照者的血清标本, 应用表面增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)联合磁珠技术, 获得蛋白质指纹图谱, 采用BPS分析软件对数据分组及相关性进行分析, 初步建立肺癌的血清蛋白质指纹图谱诊断模型, 并验证其诊断效率; 同时对比肺癌患者手术前后的差异蛋白质谱, 结合肺癌的诊断模型, 选取合适的蛋白作为肺癌手术疗效的观察指标。  结果  在质荷比为1000~50 000范围内, 肺癌患者、肺部良性肿瘤患者和正常对照者之间共检测到215个蛋白质峰。其中, 质荷比为1115.37、1929.70、3217.57、3246.34、3318.57、11 508.90的6个蛋白质峰表达差异具有统计学意义(P < 0.05)。决策树模型对肺癌的原始判别敏感性为92.11%(35/38), 特异性为90.91%(40/44);交叉验证敏感性为86.67%(13/15), 特异性为86.67%(13/15)。其中质荷比为1115.37、1929.70、3246.34和11 508.90的蛋白质峰在肺癌患者中明显升高(P < 0.05), 当肺癌患者手术治疗后表达量较术前明显降低(P < 0.01), 表明这4个蛋白质峰对肺癌的诊断及疗效判定具有潜在应用价值。  结论  应用SELDI-TOF-MS技术建立的肺癌血清蛋白质指纹图谱诊断模型具有较高的敏感性和特异性, 为发现肺癌早期生物标志物并判断疗效奠定基础。     

结直肠癌患者筛查中生化检测以及肿瘤标志物的应用价值

目的 探究结直肠癌患者筛查过程中生化检测以及肿瘤标志物的应用价值。方法 选取中国科学院合肥肿瘤医院2022年1—12月收治的91例结直肠癌患者纳入观察组,选取同期结直肠良性疾病患者91例纳入对照组,对两组使用生化检测及肿瘤标志物检测,对比两组、观察组中不同临床分期患者检验指标的差异。结果对照组TC(3.59±0.80)mmol/L、CA199(17.24±9.32)U/mL、CA72-4(1.21±6.01)U/mL、CEA(8.09±1.54)ng/mL低于观察组TC(5.19±1.64)mmol/L、CA199(21.29±11.24)U/mL、CA72-4(18.57±1.91)U/mL、CEA(60.78±24.24)ng/mL,差异有统计学意义（t=8.365、2.646、26.261、20.694,P<0.05）。观察组Ⅰ+Ⅱ期与Ⅲ+Ⅳ期的生化指标与肿瘤标志物比较,差异有统计学意义（P<0.05）。结论 在结直肠癌患者的筛查中使用生化检测以及肿瘤标志物检测方法能够拥有十分广泛的应用价值,可以用于结直肠癌筛查并可以为评估临床分期提供一定的借鉴参考价值。     

应用蛋白质芯片技术筛选直肠癌患者

目的应用表面增强激光解吸电离飞行时间质谱技术(SELDI-TOF-MS)从直肠癌患者血清中筛选标志蛋白,找出最佳的标志蛋白组合模式作为临床诊断指标。方法采用WCX2芯片及SELDI-TOF-MS技术对98例直肠癌患者及40例对照组血清进行蛋白质指纹图谱检测分析,所得到的结果采用Biomarker Wizard和Biomarker Patterns System软件分析。结果直肠癌组与对照组共有26个蛋白质差异有显著性(P<0.05);以其中4个蛋白质生物标志物(质/荷比9295、3730、3938和4095)组建筛选模型,经盲法验证,其敏感度为95.0%(57/60),特异性为93.4%(45/48);CEA敏感度为68.3%(41/60),特异性为77.1%(37/48);CA199敏感度为58.3%(35/60),特异性为75%(36/48)。结论SELDI-TOF-MS技术的敏感度和特异性远远高于目前所采用的某一单独的标志物的血清学诊断,其结果对进一步研究直肠癌的蛋白质组学改变及其临床应用可能具有重要意义。     

血清肿瘤标志物联合检验应用于结直肠癌临床诊断的价值分析

目的探讨临床诊断过程中实施血清肿瘤标志物联合检验对结直肠癌诊断效果提高的价值。方法选择2014年6月至2015年6月在海口市第三人民医院接受诊治的66例结直肠癌、66例良性病变组患者作为研究组、良性对照组,选择同期接受体检的健康人员66名作为健康对照组,对3组患者均接受血清肿瘤标志物联合检验,回顾性分析并对比检测结果。结果研究组患者血清中癌胚抗原(CEA)、糖类抗原(CA)199、CA125、CA72-4表达水平均显著高于良性对照组和健康对照组,差异有统计学意义(P0.05);联合检验的敏感度、特异度显著高于单项检验,差异有统计学意义(P0.05)。结论血清肿瘤标志物联合检验在结直肠癌诊断中具有更好的敏感度和特异度,对结直肠癌早期诊断及分期均具有重要意义。     

利用飞行质谱法对急性心肌梗死血清标志物的研究

目的利用飞行质谱法测定的蛋白质谱改变来研究诊断急性心肌梗死(AMI)的血清标志物。方法AMI病人85例,不同时段血清120份,不稳定型心绞痛病人(UP)21例,正常对照组45例。分别将所有AMI病人血清与正常对照组比较,早期AMI病人(A1)45例与正常组比较,A1组病人与UP病人比较。利用飞行质谱法测定所有血清。结果①AMI病人与正常人之间在质荷比(M/Z)813044、814984、663782、792885、329988、430755这六种蛋白质的差异呈显著性。尤其质荷比813044的蛋白质AMI病人呈明显低表达,可作为诊断AMI的血清标志物。②A1组病人与正常人之间在质荷比814984和591000这两种蛋白质的差异呈显著性。A1组病人在质荷比814984的蛋白质呈低表达,而在质荷比591000的蛋白质呈明显高表达,可作为诊断早期AMI的血清标志物。③A1组病人与UP病人之间在质荷比173436的蛋白质差异呈显著性。A1组病人在质荷比173436的蛋白质呈低表达,可作为鉴别诊断早期AMI和UP的血清标志物。结论飞行质谱方法灵敏度和特异性高,可快速、准确诊断出早期AMI,优于TnT。     

Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis

BACKGROUND: SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis. METHODS: We used SELDI-TOF MS to analyze serum samples from patients with various forms of inflammatory arthritis. Several protein profiles were collected on different Bio-Rad Laboratories ProteinChip arrays (CM10 and IMAC-Cu(2+)) and were evaluated statistically to select potential biomarkers. RESULTS: SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (SAA-RS) as biomarkers and confirmed the results with other techniques, such as western blotting, immunoprecipitation, and nano-LC-MS/MS. The S100 proteins were all able to significantly differentiate samples from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from those of patients with inflammatory bowel diseases used as an inflammatory control (IC) group, whereas the SAA, SAA-R, and SAA-RS proteins were not, with the exception of AS. The 4 S100 proteins were coproduced in all of the pathologies and were significantly correlated with the plasma calprotectin concentration; however, these S100 proteins were correlated with the SAA peak intensities only in the RA and IC patient groups. In RA, these S100 proteins (except for S100A12) were significantly correlated with the serum concentrations of C-reactive protein, matrix metalloproteinase 3, and anti-cyclic citrullinated peptide and with the Disease Activity Score (DAS(28)). CONCLUSIONS: The SELDI-TOF MS technology is a powerful approach for analyzing the status of monomeric, truncated, or posttranslationally modified forms of arthritis biomarkers, such as the S100A8, S100A9, S100A12, and SAA proteins. The fact that the SELDI-TOF MS data were correlated with results obtained with the classic calprotectin ELISA test supports the reliability of this new proteomic technique.     

Common data elements for traumatic brain injury: recommendations from the biospecimens and biomarkers working group

Manley GT, Diaz-Arrastia R, Brophy M, Engel D, Goodman C, Gwinn K, Veenstra TD, Ling G, Ottens AK, Tortella F, Hayes RL. Common data elements for traumatic brain injury: recommendations from the Biospecimens and Biomarkers Working Group.Recent advances in genomics, proteomics, and biotechnology have provided unprecedented opportunities for translational research and personalized medicine. Human biospecimens and biofluids represent an important resource from which molecular data can be generated to detect and classify injury and to identify molecular mechanisms and therapeutic targets. To date, there has been considerable variability in biospecimen and biofluid collection, storage, and processing in traumatic brain injury (TBI) studies. To realize the full potential of this important resource, standardization and adoption of best practice guidelines are required to insure the quality and consistency of these specimens. The aim of the Biospecimens and Biomarkers Working Group was to provide recommendations for core data elements for TBI research and develop best practice guidelines to standardize the quality and accessibility of these specimens. Consensus recommendations were developed through interactions with focus groups and input from stakeholders participating in the interagency workshop on Standardization of Data Collection in TBI and Psychological Health held in Washington, DC, in March 2009. With the adoption of these standards and best practices, future investigators will be able to obtain data across multiple studies with reduced costs and effort and accelerate the progress of genomic, proteomic, and metabolomic research in TBI.     

CT colonography: surveillance in patients with a history of colorectal cancer

Colorectal cancer is a leading cause of morbidity and mortality in the United States. It is also a disease that is preventable if precursor adenomatous polys are removed. Once a diagnosis of colorectal cancer is made, surgical resection is the only means of cure. The ability to resect colorectal cancer for cure is largely dependent upon the stage of tumor at presentation. Once a patient has been treated for colorectal cancer with surgery and in some cases neo-adjuvant or adjuvant therapy, they will present for follow-up. Surveillance is performed on these patients in order to detect local recurrence that if detected early can be surgically resected for cure. Surveillance also allows detection of distant metastatic disease that may in some cases also be cured with resection. Finally, surveillance of the remaining colon is important to detect the development of new or metachronous adenomatoid polyps that if left in place could develop into new colon cancers. Imaging can play a part in patient surveillance to detect recurrent disease at extracolonic sites as well as the development of new colonic lesions. CT colonography is a promising tool for surveillance in patients with a history of colorectal cancer.     

microRNA在结直肠癌研究中的新进展

microRNA（miRNA）是一类长约22~25个核苷酸的内源性非编码调控RNA,可参与细胞发育、增殖、分化和凋亡.miRNA具有癌基因和抑癌基因的作用,若干miRNA直接或间接参与结直肠癌的发生和发展,miRNA表达谱与结直肠癌的诊断、分期、进展和预后密切相关,为结直肠癌的早期发现和治疗起到一定的理论指导作用,将为结直肠癌的治疗提供新的策略和方法.     

肝X受体激动剂GW3965对人结肠癌细胞增殖的抑制作用

目的:探讨激活肝X受体(liver X receptors,LXRs)对人结肠癌细胞增殖的影响。方法:采用实时定量聚合酶链反应检测人结肠癌细胞HCT116和Lovo中LXRα和LXRβ的mRNA表达;LXRs激动剂GW3965分别处理2种细胞后,以CCK-8法检测细胞生长曲线的变化,流式细胞仪检测细胞增殖周期的变化,蛋白印迹法检测AMPK、mTOR和p70S6K蛋白及相应磷酸化蛋白的表达变化。结果 :设定LXRαmRNA在HCT116细胞的表达水平为1,LXRβmRNA在HCT116和Lovo细胞中的相对表达量分别是LXRαmRNA在HCT116细胞表达水平的3.1倍和4.6倍。经10μmol/L和20μmol/L的GW3965处理48 h及72 h后,2种结肠癌细胞的生长都受到明显抑制(P<0.05);相应G1~G0期细胞百分比显著增多,而S期细胞百分比明显减少(P<0.01);磷酸化AMPK蛋白(p-AMPK)的表达水平在HCT116和Lovo细胞中分别上升了2.97倍和3.48倍(P<0.05);p-mTOR和p-p70S6K在HCT116细胞中的表达分别下降了33.14%和38.44%,在Lovo细胞中的表达分别下降了51.68%和31.52%(P<0.05)。结论:激活LXRs可通过干预细胞周期和AMPK-mTOR-S6K信号通路抑制结肠癌细胞增殖。     

结肠癌组织中SATB1的表达及其临床意义

目的探讨SATB1异常表达与结肠癌发生、发展及预后的关系。方法分别用RT-PCR和Western blot法检测SATB1在25例结肠癌活检组织及相应癌旁正常组织中mRNA和蛋白表达水平;采用免疫组化检测58例结肠癌石蜡组织切片中SATB1的表达,分析其与结肠癌临床病理因素的关系及预后意义。结果 SATB1 mRNA和蛋白在92%(23/25)结肠癌活检组织中的表达水平高于其癌旁正常组织;58例结肠癌石蜡组织中,SATB1蛋白强阳性率为46.6%(27/58)。统计学分析结果显示,SATB1强阳性与结肠癌Dukes分期和远处转移密切相关,而与性别、年龄、病理分级、肿瘤大小、淋巴结转移无显著相关性。结论 SATB1在结肠癌中高表达,其表达水平与肿瘤进展相关,可作为预测结肠癌进展和转移的分子标记物。