低剂量螺旋CT联合肺癌自身抗体、肿瘤标志物CA12-5、CA19-9在肺癌诊断中的临床应用价值

摘要 目的：探讨低剂量螺旋CT联合肺癌自身抗体、肿瘤标志物糖类抗原（CA）12-5、CA19-9在肺癌诊断中的临床应用价值。方法：选择2019年1月至2021年12月在我院经低剂量螺旋CT检查发现肺部病灶的患者86例,以病理诊断结果分为肺癌组49例、肺部良性病变组37例,另选取同期健康体检志愿者30例作为对照组。观察肺癌的低剂量螺旋CT影像学特征,检测比较各组血清肺癌自身抗体[p53、SOX区域Y相关HMG蛋白家族成员2（SOX2）、G抗原7（GAGE7）、RNA解旋酶自身抗体4-5（GBU4-5）]及CA12-5、CA19-9水平,并对比阳性表达情况,分析低剂量螺旋CT联合肺癌自身抗体、CA12-5、CA19-9对肺癌的诊断价值。结果：49例肺癌患者经低剂量螺旋CT检查共发现51个病灶,其中实性结节或部分实性结节30个,非实性结节21个;病灶平均直径（10.92±1.17）mm,＜5 mm者9个,5～10 mm者17个,≥10 mm者25个;11个病灶伴有钙化,16个病灶有毛刺征,20个病灶有分叶征;有6例表现为空洞,空洞通常壁薄厚不均匀,呈中心性或偏心性。肺癌组血清p53、SOX2、GAGE7、GBU4-5及CA12-5、CA19-9水平均明显高于肺部良性病变组和对照组,肺部良性病变组上述指标水平均明显高于对照组（P<0.05）。肺癌组CA12-5、CA19-9、4项肺癌自身抗体单独及联合的阳性率均明显高于肺部良性病变组和对照组（P<0.05）,肺部良性病变组CA12-5、CA19-9及4项肺癌自身抗体联合的阳性率高于对照组（P<0.05）。低剂量螺旋CT联合4项肺癌自身抗体、CA12-5、CA19-9对肺癌诊断的灵敏度为91.84%,特异度为97.30%,准确度为94.19%。结论：低剂量螺旋CT联合肺癌自身抗体、肿瘤标志物CA12-5、CA19-9在肺癌诊断中有较好的临床应用价值。     

评价抗SSA、抗SSB 和抗a- 胞衬蛋白抗体在诊断干燥 综合征中的价值

目的：评价SSA、SSB 和胞衬蛋白在诊断干燥综合征(SS)中的价值。方法：用酶联免疫吸附试验（ELISA）检测47 例确诊为SS 患者、20 例其它自身免疫病(类风湿关节炎7 例、SLE6 例、自身免疫性肌炎7 例)和20 例体检健康者血清抗SSA、SSB 和a- 胞衬 蛋白抗体,分析三种自身抗体阳性率。结果：抗SSA抗体、抗SSB 抗体和抗a-胞衬蛋白抗体敏感性分别为76.6%、38.3%、42.6%; 特异性分别为72.5%、95.0%、82.5%;三种抗体联合检测后敏感性为89.4%,特异性50.0%。结论：抗a- 胞衬蛋白抗体与抗SSA、 SSB 抗体联合检测时可提高阳性率,对症状不典型的SS 患者诊断有一定的补充意义。     

葡萄糖-6-磷酸异构酶抗原对类风湿关节炎的诊断价值

目的:通过比较类风湿关节炎(Rheumatoid arthritis,RA)患者、非RA风湿病患者及健康对照者血清中葡萄糖-6-磷酸异构酶(glucose-6-phosphate isomerase,GPI)抗原的阳性率来探讨GPI对RA的诊断意义,并探讨GPI,抗CCP抗体和RF联合应用对RA的诊断价值.方法:对110例RA患者、223例非RA风湿病患者和55例健康对照者共388份血清标本进行了检测.GPI抗原和抗CCP抗体采用ELISA方法,RF采用免疫比浊法定量检测.结果:RA组、非RA风湿病组和健康对照组血清中的GPI抗原阳性率分别为83.64%,30.04%和20.00%,RA组阳性率显著高于其它组(P＜0.01).GPI抗原对RAt诊断的敏感性和特异性分别为83.64%和71.58%.GPI和抗CCP抗体联合检测的敏感性和特异性分别为90.91%和71.22%,GPI和RF联合检测的敏感性和特异性分别为92.73%和 61.87%,如果三者同时检测,其敏感性和特异性分别为94.55%和60.43%.结论:RA患者的血清GPI阳性率明显高于其它自身免疫性疾病患者和健康对照者.GPI抗原时RA具有诊断价值,联合检测GPI、抗CCP抗体和RF可以提高RA诊断的敏感性.     

评价抗SSA、抗SSB和抗α-胞衬蛋白抗体在诊断干燥综合征中的价值

目的：评价SSA、SSB和胞衬蛋白在诊断干燥综合征（SS）中的价值。方法：用酶联免疫吸附试验（ELIsA）检测47例确诊为SS患者、20例其它自身免疫病（类风湿关节炎7例、SLE6例、自身免疫性肌炎7例）和20例体检健康者血清抗SSA、SSB和α-胞衬蛋白抗体,分析三种自身抗体阳性率。结果：抗SSA抗体、抗SSB抗体和抗仅．胞衬蛋白抗体敏感性分别为76．6％、38．3％、42．6％;特异性分别为72．5％、95．0％、82．5％;三种抗体联合检测后敏感性为89．4％,特异性50．0％。结论：抗仪．胞衬蛋白抗体与抗SSA、SSB抗体联合检测时可提高阳性率,对症状不典型的SS患者诊断有一定的补充意义。     

GICA和CLIA联合检测SARS-CoV-2特异性抗体的检测策略研究

评价胶体金免疫层析法(GICA)与化学发光法(CLIA)联合检测对降低新型冠状病毒(SARS-CoV-2)特异性抗体假阳性的效果。收集2020年1月22日至2020年3月5日就诊于川北医学院附属医院及南充市中心医院的19例SARS-CoV-2确诊患者不同时段的血清33份,55例非SARS-CoV-2、其他病原体感染及自身免疫性疾病患者的血清55份,采用GICA和CLIA分别对血清SARS-CoV-2 IgM、IgG进行检测,并对结果进行分析。GCIA检测SARS-CoV-2 IgM、IgG的敏感性分别为100.0%、94.74%,与CLIA(92.86%和100.0%)比较没有差异(P>0.05);GCIA检测SARS-CoV-2 IgM、IgG的特异性分别为70.91%、74.55%,明显低于CLIA的特异性(98.18%和89.09%)(P<0.01);两种方法检测SARS-CoV-2 IgM、IgG结果具有一致性(P<0.001),Kappa值分别为0.434,0.406;ROC曲线分析发现,GCIA检测SARS-CoV-2 IgM、IgG的AUC分别为0.855、0.846,明显低于CLIA(0.955和0.945)(P<0.05)。两种方法联合检测SARS-CoV-2 IgM、IgG的敏感性分别为92.86%、94.74%,特异性分别为100.0%、100.0%;ROC曲线分析显示,联合检测SARS-CoV-2 IgM、IgG的AUC分别为0.964、0.974,高于两种方法的单独检测。GICA和CLIA联合检测能有效提高SARS-CoV-2 IgM和IgG的检测特异性,值得临床推广应用。     

抗SmD1抗体对系统性红斑狼疮诊断的临床意义

目的探讨抗SmD1抗体的测定对系统性红斑狼疮(SLE)诊断的临床意义。方法用免疫学方法分别检测SLE患者90例、非SLE病例对照组患者100例及健康对照组患者70例血清中的自身抗体。抗SmD1抗体的检测用ELISA方法;抗Sm抗体、抗双链DNA(dsDNA)抗体、抗核小体抗体(ANuA)的检测用免疫印迹法。结果 SLE组患者血清中抗SmD1抗体阳性率为75.6%;抗ANuA抗体阳性率为56.7%;抗Sm抗体的阳性率为24.4%;抗dsDNA抗体阳性率为47.8%。SmD1抗体阳性率明显高于ANuA抗体、Sm抗体及dsDNA抗体,差异有统计学意义(P0.05),且抗SmD1抗体的特异性为98.2%。结论与传统的检测指标比较,抗SmD1抗体具有较高的敏感性和特异性,可作为诊断SLE的一项重要的特异性检测指标。     

肺癌诊断方法的比较与研究进展

近年来,随着周围环境的恶化,肺癌的发病率最高并且呈现逐年上升的趋势,且其早期表现隐匿,很容易被忽视,很多患者确诊时已属晚期,丧失去了治疗的最佳时机。.本文主要总结和比较了几种传统的肺癌诊断方法如X线片、CT、MRI、PET-CT,并介绍了几种肺癌的最新的诊断技术,比如肺泡灌洗液或血清肿瘤标记物的联合检测、呼出气中的有机化合物的构成分析以及纤维支气管镜镜检技术等。上述方法诊断肺癌的敏感性和特异性各有优势,临床医生在临床工作中应合理应用上述检测方法,必要时联用多种检测手段,尤其要重视支气管肺泡灌洗液癌胚抗原如Cyfra21-1和CEA的联合检测,利用其较高的敏感性以提早发现和诊断肺癌。     

血清PCT联合血浆1,3-β-D-葡聚糖检测对自身免疫性疾病合并侵袭性肺真菌病的诊断价值

目的探讨血清降钙素(PCT)联合血浆1,3-β-D-葡聚糖检测对自身免疫性疾病(AID)合并侵袭性肺真菌病的诊断价值。方法选取医院收治的AID合并侵袭性肺真菌感染患者45例作为病例组,选取同收治的AID患者50例作为对照组,检测两组血清PCT和血浆1,3-β-D-葡聚糖水平,利用受试者工作特征曲线(ROC)评价血清PCT和血浆1,3-β-D-葡聚糖对自身免疫性疾病合并侵袭性肺真菌病的诊断价值。结果病例组血清PCT联合血浆1,3-β-D-葡聚糖水平均高于对照组,差异有统计学意义(P0.05);绘制ROC曲线,血清PCT的诊断截点为0.05ng/mL,AUC为0.713,血浆1,3-β-D-葡聚糖诊断截点为20ng/mL,AUC为0.851,两者联合诊断的AUC为0.936。两者联合诊断AID合并侵袭性肺真菌病的准确性、敏感性、特异性分别为92.63%、93.33%、92.0%,显著高于血清PCT检测的72.63%、72.63%、76.0%,差异有统计学意义(P0.05),两者联合诊断的准确高于血浆1,3-β-D-葡聚糖诊断的81.05%(P0.05),其余比较差异无统计学意义(P0.05)。结论血清PCT联合血浆1,3-β-D-葡聚糖检测对AID合并侵袭性肺真菌病有较好的诊断效能。     

应用双向热循环消减SELEX技术筛选肺癌血清核酸适配体

肺癌是发病率和死亡率较高的恶性肿瘤。现阶段,用于肺癌早期诊断的血清肿瘤标志物因其特异性与敏感性均较低,严重影响肺癌的临床诊断和治疗。本文用双向热循环消减指数富集的配基进化(systematic evolution of ligands by exponential enrichment, SELEX)技术,筛选肺癌和非癌血清标志物的核酸适配体,建立肺癌的检测方法,提高诊断和治疗效率。实验用环氧基琼脂磁珠为筛选介质,以非癌混合血清、肺癌混合血清作为双向靶标。应用热循环消减SELEX技术,经19轮筛选分别获得非癌和肺癌血清的特异性核酸适配体。通过高通量测序,得到 40条非癌核酸适配体序列和 41条肺癌核酸适配体序列。从肺癌与非癌血清特异性核酸适配体序列中分别挑选出高丰度的 4条序列,合成后制成检测试剂,经临床血清验证,阳性率为 90%。该检测方法检测灵敏度高,为肺癌的早期诊断和治疗提供了新的分子识别元件。     

免疫-PCR法检测梅毒螺旋体特异性抗体

以梅毒螺旋体重组蛋白为抗原,应用免疫-PCR方法检测梅毒螺旋体抗体,并同常规ELISA法进行比较,探讨免疫-PCR方法检测梅毒螺旋体特异性抗体的可行性。结果免疫-PCR法敏感性是常规ELISA法的104倍,阳性检出率高于ELISA法;对照血清标本梅毒螺旋体抗体检测为阴性。表明免疫-PCR方法具有较高敏感性和特异性,有一定的临床推广价值,对梅毒患者的早期诊断及时治疗等具有重要意义。     

Early Detection of NSCLC with scFv Selected against IgM Autoantibody

Survival of patients with lung cancer could be significantly prolonged should the disease be diagnosed early. Growing evidence indicates that the immune response in the form of autoantibodies to developing cancer is present before clinical presentation. We used a phage-displayed antibody library to select for recombinant scFvs that specifically bind to lung cancer-associated IgM autoantibodies. We selected for scFv recombinant antibodies reactive with circulating IgM autoantibodies found in the serum of patients with early stage lung adenocarcinoma but not matched controls. Discriminatory performance of 6 selected scFvs was validated in an independent set of serum from stage 1 adenocarcinoma and matching control groups using two independent novel methods developed for this application. The panel of 6 selected scFvs predicted cancer based on seroreactivity value with sensitivity of 0.8 and specificity of 0.87. Receiver Operative Characteristic curve (ROC) for combined 6 scFv has an AUC of 0.88 (95%CI, 0.76–1.0) as determined by fluorometric microvolume assay technology (FMAT) The ROC curve generated using a homogeneous bridging Mesa Scale Discovery (MSD) assay had an AUC of 0.72 (95% CI, 0.59–0.85). The panel of all 6 antibodies demonstrated better discriminative power than any single scFv alone. The scFv panel also demonstrated the association between a high score - based on seroreactivity - with poor survival. Selected scFvs were able to recognize lung cancer associated IgM autoantibodies in patient serum as early as 21 months before the clinical presentation of disease. The panel of antibodies discovered represents a potential unique non-invasive molecular tool to detect an immune response specific to lung adenocarcinoma at an early stage of disease.     

Identification of Novel Autoantibodies for Detection of Malignant Mesothelioma

Background

The malignant mesothelioma (MM) survival rate has been hampered by the lack of efficient and accurate early detection methods. The immune system may detect the early changes of tumor progression by responding with tumor-associated autoantibody production. Hence, in this study, we translated the humoral immune response to cancer proteins into a potential blood test for MM.

Methodology/Principal Findings

A T7 phage MM cDNA library was constructed using MM tumor tissues and biopanned for tumor-associated antigens (TAAs) using pooled MM patient and normal serum samples. About 1008 individual phage TAA clones from the biopanned library were subjected to protein microarray construction and tested with 53 MM and 52 control serum samples as a training group. Nine candidate autoantibody markers were selected from the training group using Tclass system and logistic regression statistical analysis, which achieved 94.3% sensitivity and 90.4% specificity with an AUC value of 0.89 in receiver operating characteristic analysis. The classifier was further evaluated with 50 patient and 50 normal serum samples as an independent blind validation, and the sensitivity of 86.0% and the specificity of 86.0% were obtained with an AUC of 0.82. Sequencing and BLASTN analysis of the classifier revealed that five of these nine candidate markers were found to have strong homology to cancer related proteins (PDIA6, MEG3, SDCCAG3, IGHG3, IGHG1).

Conclusions/Significance

Our results indicated that using a panel of 9 autoantibody markers presented a promising accuracy for MM detection. Although the results need further validation in high-risk groups, they provided the potentials in developing a serum-based assay for MM diagnosis.     

Biomarkers for screening of lung cancer and pre-neoplastic lesions in a high risk Chilean population

Background

The mortality of lung cancer (LC), increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 μg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70) and Auto Fluorescence Bronchoscopy (AFB) might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL) and neoplastic lesions (NL).

Results

Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8%) and specificity (91.9%) than AQC. However, for PNL AQC showed a higher sensitivity (91.9%) than DR70 (27.3%), although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%).

Conclusion

This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC. Supported by INNOVA-CORFO, Chile.     

Application of a High Throughput Method of Biomarker Discovery to Improvement of the EarlyCDT?-Lung Test

Background

The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT.Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)).

Methods and Findings

Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7).

Conclusion

This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT­-Lung test, and so further aid the early detection of lung cancer.     

血清PCT、CRP与sTREM-1在肺癌患者术后肺部感染中表达及其诊断价值分析

目的:探究血清降钙素原(PCT)、C-反应蛋白(CRP)与可溶性人髓系细胞触发受体-1(sTREM-1)在肺癌患者术后肺部感染中表达及其诊断价值。方法:选择2016年2月至2019年10月期间在我院行肺癌根治术的420例肺癌患者作为研究对象,根据术后患者是否发生肺部感染进一步划分为380例未感染组和40例感染组。感染组根据治疗结局进一步划分为29例治疗好转亚组与11例未好转亚组。采用酶联免疫吸附法检测各组的血清PCT、CRP与s TREM-1水平,采用受试者工作特征(ROC)曲线分析血清PCT、CRP和s TREM-1对肺癌患者术后肺部感染的预测价值。结果:与未感染组相比,感染组手术后血清PCT、CRP和s TREM-1水平均明显升高(P0.05)。与治疗好转亚组相比较,治疗未好转亚组手术后以及感染后血清PCT、CRP和s TREM-1水平均明显升高(P0.05)。ROC曲线显示,PCT的曲线下面积(AUC)为0.713,最佳截断值为1.23 ng/mL,灵敏度、特异度分别为0.81、0.79,准确度为0.82;CRP的AUC为0.752,最佳截断值为36.07 mg/L,灵敏度、特异度分别为0.83、0.81,准确度为0.83;s TREM-1的AUC为0.792,最佳截断值为20.58 pg/mL,灵敏度、特异度分别为0.86、0.84,准确度为0.85;PCT、CRP联合s TREM-1预测肺癌患者术后肺部感染的AUC为0.884,灵敏度、特异度分别为0.89、0.91,准确度为0.92。结论:肺癌根治术后肺部感染发生与患者血清PCT、CRP和s TREM-1水平相关,早期联合检测血清PCT、CRP和s TREM-1有助于预测肺癌根治术患者肺部感染发生风险,在肺癌根治术后肺部感染的预测和诊断中具有一定临床价值。     

彩色多普勒超声联合血清CEA、CA125、TK1、TFF1对乳腺癌的诊断价值研究

摘要 目的：探究彩色多普勒超声联合血清癌胚抗原（CEA）、糖类抗原125（CA125）、胸苷激酶1（TK1）、三叶因子1（TFF1）对乳腺癌的诊断价值。方法：回顾性选取2019年1月到2022年1月间我院收治的97例乳腺癌患者为观察组,同期收治的97例乳腺良性病变患者为对照组,均行彩色多普勒超声检查及血清CEA、CA125、TK1、TFF1检测,比较两组超声特征、超声参数[搏动指数（PI）、收缩期峰值流速（PSV）、阻力指数（RI）],比较两组血清CEA、CA125、TK1、TFF1水平,通过受试者工作特征（ROC）曲线分析彩色多普勒超声联合血清CEA、CA125、TK1、TFF1诊断价值及单独诊断价值。结果：与对照组比较,观察组肿块边界不清晰、内部回声不均匀、形态不规则和钙化比例明显升高（P＜0.05）。与对照组比较,观察组患者RI、PSV、PI明显升高（P＜0.05）;其中观察组血流信号分级Ⅲ级比例明显高于对照组（P＜0.05）,观察组血流信号分级0级比例明显低于对照组（P＜0.05）。与对照组比较,观察组患者血清CEA、CA125、TK1、TFF1水平明显升高（P＜0.05）。ROC曲线发现,超声诊断乳腺癌的曲线下面积（AUC）值、灵敏度、特异度依次为0.773、76.30%、78.40%。CEA诊断乳腺癌的AUC值、灵敏度、特异度依次为0.774、78.40%、74.23%。CA125诊断乳腺癌的AUC值、灵敏度、特异度依次为0.824、77.31%、80.41%。TK1诊断乳腺癌的AUC值、灵敏度、特异度依次为0.818、78.43%、81.42%。TFF1诊断乳腺癌的AUC值、灵敏度、特异度依次为0.806、78.42%、77.31%。彩色多普勒超声联合血清CEA、CA125、TK1、TFF1诊断乳腺癌的AUC值0.929,显著优于各项指标单独使用（P＜0.05）。结论：与各项指标单一应用相比,彩色多普勒超声联合血清CEA、CA125、TK1、TFF1诊断乳腺癌的价值较高,有助于乳腺癌的早期筛查。     

Autoantibody biomarker opens a new gateway for cancer diagnosis

The list of cancer markers of current interest has grown considerably, but none of the markers used in clinical work is a true tumor marker. These cancer biomarkers are based on the determination of tumor antigens. Here, we report a single method of autoantibody enzyme immunoassay (EIA) screens for a spectrum of serum tumor markers. A comparison of the autoantibody-based EIA to conventional antigen EIA kits, using receiver operating characteristic (ROC) plots, showed that the autoantibody EIA can significantly enhance the sensitivity and specificity of tumor markers. The detection of serum autoantibodies for a spectrum of serum tumor markers, as demonstrated here, suggests that most, if not all, serum cancer biomarkers produce autoantibodies. A unique autoantibody biomarker screening method, as presented here, might therefore facilitate achieving the accurate and early diagnosis of cancer.     

CT联合DR对早期周围型肺癌的诊断价值

目的:分析数字X线摄片(DR)、CT及其联合应用对周围型肺癌的诊断价值。方法:选择该院2012年2月~2016年3月收治早期周围型肺癌患者90例为研究对象,分别进行数字化X线摄影和CT检查,以手术切除或病理结果为最终诊断的金标准,计算两种检查方法及其联合对早期诊断周围型肺癌的敏感度、特异度和准确率阳性预测值以及阴性预测值。结果:胸部DR检出空泡征者7例(7.8%),分叶征47例(52.2%),边缘有细小毛刺征36例(40%),胸膜凹陷征9例(10%);CT见病变边缘分叶征71例(78.8%),长短毛刺征57例(63.3%),空洞征27例(30%),胸膜凹陷征32例(35.6%)。DR诊断周围型肺癌的敏感性、特异性及准确性分别为85%、81%、85.6%,而CT则为90%,87.6%,90.5%,均高于DR。DR与CT两者联合诊断周围型肺癌的敏感性为98.4%,显著高于DR(85%)和CT(90%)。结论:在早期周围型肺癌的影像学诊断中,CT的临床价值显著优于DR,而两者联合诊断的临床价值明显优于单独检测。     

Tumor-associated antigen arrays for the serological diagnosis of cancer

The recognition that human tumors stimulate the production of autoantibodies against autologous cellular proteins called tumor-associated antigens (TAAs) has opened the door to the possibility that autoantibodies could be exploited as serological tools for the early diagnosis and management of cancer. Cancer-associated autoantibodies are often driven by intracellular proteins that are mutated, modified, or aberrantly expressed in tumor cells and hence are regarded as immunological reporters that could help uncover molecular events underlying tumorigenesis. Emerging evidence suggests that each type of cancer might trigger unique autoantibody signatures that reflect the nature of the malignant process in the affected organ. The advent of novel genomic, proteomic, and high throughput approaches has accelerated interest in the serum autoantibody repertoire in human cancers for the discovery of candidate TAAs. The use of individual anti-TAA autoantibodies as diagnostic or prognostic tools has been tempered by their low frequency and heterogeneity in most human cancers. However, TAA arrays comprising several antigens significantly increase this frequency and hold great promise for the early detection of cancer, monitoring cancer progression, guiding individualized therapeutic interventions, and identification of novel therapeutic targets. Our recent studies suggest that the implementation of TAA arrays in screening programs for the diagnosis of prostate cancer and other cancers should be preceded by the optimization of their sensitivity and specificity through the careful selection of the most favorable combinations of TAAs.     

Autoantibodies against tumor-associated antigens in sputum as biomarkers for lung cancer

Tumor antigens (TAs) can initiate host immune responses and produce TA-associated autoantibody (TAAbs), potential cancer biomarkers. Sputum is directly generated from the upper and lower airways, and thus can be used as a surrogate sample for the diagnosis of lung cancer based on molecular analysis. To develop sputum TAAb biomarkers for the early detection of lung cancer, the leading cause of cancer death, we probed a protein microarray containing more than 9,000 antigens with sputum supernatants of a discovery set of 30 lung cancer patients and 30 cancer-free smokers. Twenty-eight TAs with higher reactivity in sputum of lung cancer cases vs. controls were identified. The diagnostic significance of TAAbs against the TAs was determined by enzyme-linked immunosorbent assays (ELISAs) in sputum of the discovery set and additional 166 lung cancer patients and 213 cancer-free smokers (validation set). Three sputum TAAbs against DDX6, ENO1, and 14–3-3ζ were developed as a biomarker panel with 81% sensitivity and 83% specificity for diagnosis of lung cancer, regardless of stages, locations, and histological types of lung tumors. This study provides the first evidence that sputum TAAbs could be used as biomarkers for the early detection of lung cancer.