p53等七种肿瘤相关抗体在肺癌早期诊断中的意义

发布时间：2018-03-24 13:19

本文选题：肿瘤相关抗体　切入点：肺癌　出处：《大连医科大学》2017年硕士论文

【摘要】：研究目的本文探究一组新肿瘤相关抗体(包括p53,NY-ESO-1,CAGE,GBU4-5,SOX2,Hu D,及MAGEA1抗体)对肺癌早期诊断的意义。同时讨论分析患者相关临床因素对自身抗体水平有无影响。研究方法选取2015年11月至2016年4月期间在大连医科大学附属二院因咳嗽、咯血、胸闷等症状或因体格检查行多排螺旋CT,同时对肺内病灶行手术切除或取活检后行病理确认的患者。根据患者多排螺旋CT结果有无病灶及病灶病理结果,确定为肺癌组(n=397),良性病灶组(n=45)及健康对照组(n=74)。应用酶联免疫吸附测定法,分别测定三组样本血清中七种抗体水平,同时收集三组样本四种传统肿瘤标志物水平(包括CEA、SCC、CYFRA211、NSE)。七个肿瘤相关抗体中只要任意一个大于它的临界值,即认定该患者肿瘤相关抗体组合为阳性。四个传统肿瘤标志物中只要任意一个大于它的临界值,即认定该患者传统肿瘤标志物组合为阳性。分别比较单个抗体与联合七种肿瘤相关抗体对于肺癌诊断的敏感性、特异性;分析肺癌患者不同临床资料(病理类型、TNM分期、病灶大小)对抗体水平有无影响。同时比较联合七种肿瘤相关抗体与联合四种传统肿瘤标志物对于不同TNM分期非小细胞肺癌诊断的敏感性、特异性。研究结果1.在肺癌组,联合七种肿瘤相关抗体所测定出的阳性率(56.53%)显著高于良性病灶组(11.11%)及健康对照组(6.76%),差异有统计学意义(c(17)=83.681,P=0.000);且在肺癌组,联合七种肿瘤相关抗体所测定出的阳性率明显较单个抗体阳性率高,差异均有统计学意义(P均0.05)。联合七种肿瘤相关抗体得出的诊断特异性为91.60%。该组抗体对肺癌患者的阳性预测值较高,为95.80%;同时阴性预测值为45.42%。2.联合七种肿瘤相关抗体得出的诊断特异性为91.60%。当结合健康对照组的CT结果后,诊断的特异性可以进一步提高到95.80%。3.在不同病理类型肺癌间,联合七种肿瘤相关抗体所测得的阳性值差异无统计学意义(P=0.507)。对于非小细胞肺癌,联合七种肿瘤相关抗体检测,I期患者阳性率56.39%,II期为57.14%,III期为55.81%,IV为56.32%,不同病程分期患者之间联合七种肿瘤相关抗体所测的阳性率差异亦无统计学意义(P=0.999)。对于小细胞肺癌,联合七种肿瘤相关抗体检测,小细胞肺癌扩散期的阳性率(72.00%)显著高于小细胞肺癌局限期患者(40.91%),差异有统计学差异(c2=4.627,P=0.031)。同时在不同病灶大小肺癌患者之间,联合七种肿瘤相关抗体检测,≤8mm患者阳性率56.67%,8-20mm为55.13%,20-30mm为52.46%,≥30mm为57.89%,超过一个病灶的患者为61.29%,虽然大于30mm病灶阳性率高于小于8mm的病灶,但阳性率的差异无统计学意义(P=0.928)。4.使用ROC曲线分析联合七种肿瘤相关抗体及联合四种传统肿瘤标志物检测对于不同分期非小细胞肺癌诊断的敏感性、特异性、AUC值,对于I、II期非小细胞肺癌,联合四种传统肿瘤标志物所得出的AUC值为0.799,联合七种肿瘤相关抗体所得出的AUC值为0.746,AUC值的差异无统计学意义(P0.05)。对于I、II期非小细胞肺癌,联合七种肿瘤相关抗体测得诊断敏感性为56.57%,特异性91.60%,将联合四种传统肿瘤标志物所测得的诊断特异性取值为91.60%时,其诊断敏感性只有33.10%,敏感性低于联合七种肿瘤相关抗体,且差异有统计学意义(P=0.012)。对于III、IV期肺癌,联合四种传统肿瘤标志物测得的AUC值为0.959,联合七种肿瘤相关抗体测得的AUC值为0.710,联合四种传统肿瘤标志物测得的AUC值高于联合七种抗体,且差异有统计学意义(P=0.001)。对于III、IV期肺癌,联合七种肿瘤相关抗体所测得的敏感性为56.15%,为特异性91.60%,将联合四种传统肿瘤标志物的诊断特异性取值为91.60%时,其诊断的敏感性可到达90.80%,敏感性高于联合七种抗体,且差异有统计学意义(P=0.000)。研究结论认为一组新肿瘤相关抗体可以作为早期肺癌诊断一种新方法,其具有较高的敏感性及特异性。不同组织学类型、非小细胞肺癌病程分期、病灶大小对自身抗体水平无影响。
[Abstract]:The purpose of this study to explore a new group of tumor associated antibodies (including p53, NY-ESO-1, CAGE, GBU4-5, SOX2, Hu, D, and MAGEA1 antibody) in early diagnosis of lung cancer. At the same time to discuss the related clinical factors of patients have no effect on antibody levels. Methods from November 2015 to April 2016 in the Second Affiliated Hospital of Dalian Medical University during the period due to cough hemoptysis, chest tightness and other symptoms, or multi row spiral CT for physical examination, the lung lesions underwent surgical resection or biopsy confirmed by pathology of patients. According to the results of multi slice spiral CT with the lesions and pathological results, identified as lung cancer group (n=397), benign lesions (n=45) and healthy control group group (n=74). The enzyme-linked immunosorbent assay, seven antibody levels of three samples of serum were measured, and collected three samples of four kinds of traditional tumor marker level (including CEA, SCC, CYFRA211, N SE). Seven tumor associated antibodies as long as any one is larger than its critical value, namely that the patients with tumor related antibody combinations were positive. Four traditional tumor markers as long as any one is larger than its critical value, namely that the patients with traditional tumor markers combination was positive. Compared to single antibody combined with seven kinds of antibodies to tumor sensitivity and specificity in the diagnosis of lung cancer; analysis of lung cancer patients with different clinical data (pathological type, TNM staging, lesion size) of antibody level has no effect. At the same time, compared with seven kinds of tumor associated antibodies combined with four traditional tumor markers for different TNM staging of non small cell sensitivity, diagnosis lung cancer specificity. Results 1. in lung cancer group, the positive rate of combined seven kinds of tumor associated antibodies measured (56.53%) was significantly higher than that in benign lesion group (11.11%) and control group (6.76%), the difference There was statistical significance (C (17) =83.681, P=0.000); and in the lung cancer group, the positive rate of combined seven kinds of tumor related antibody detected obviously than single antibody positive rate is high, the differences were statistically significant (P < 0.05). The diagnostic specificity combined with seven kinds of tumor associated antibodies obtained for the positive predictive 91.60%. group of antibodies in patients with lung cancer was higher for 95.80%; while the negative predictive value of diagnostic specificity that combined with seven kinds of tumor associated antibodies to 45.42%.2. 91.60%. when combined with CT results in healthy control group, the diagnostic specificity can be further increased to 95.80%.3. in different pathological types of lung cancer, combined with seven kinds of tumor associated antibodies the measured value was no statistically significant difference (P=0.507). For non small cell lung cancer, combined detection of seven tumor associated antibody I positive rate were 56.39%, II 57.14%, III 55.81%, IV 56.32%, different The positive rate of the difference between the staging patients combined with seven kinds of tumor associated antibodies tested and there was also no significant difference (P=0.999). For small cell lung cancer, combined detection of seven tumor associated antibody, the positive rate of small cell lung cancer diffusion stage (72%) was significantly higher than that of small cell lung cancer patients with Limited (40.91%), the difference was statistically significant (c2=4.627, P=0.031). At the same time between patients with different lesion size of lung cancer, combined detection of seven tumor associated antibodies, less than the positive rate of serum 8mm 56.67%, 8-20mm 55.13%, 20-30mm 52.46%, 30mm = 57.89%, more than one lesion of patients was 61.29%, while the positive rate of 30mm was higher than that of larger than lesions less than 8mm lesions. But there was no significant difference between the positive rate (P=0.928) analysis of markers for different stage diagnosis of non small cell lung cancer combined with seven kinds of tumor associated antibodies and the combination of the four traditional tumor.4. using ROC curve The sensitivity, specificity, AUC values for I, II stage non-small cell lung cancer, combined with four kinds of traditional tumor markers derived from the AUC value of 0.799, combined with seven kinds of tumor associated antibodies derived from the AUC value of 0.746, there were no significant differences in AUC values (P0.05). For I, II stage small cell lung cancer, combined with seven kinds of tumor associated antibodies measured diagnostic sensitivity was 56.57%, specificity of 91.60%, will be combined with four kinds of traditional tumor marker values measured by the diagnostic specificity was 91.60%, the diagnostic sensitivity was 33.10%, the sensitivity is lower than the combined seven kinds of tumor associated antibodies, and the difference was statistically significant (P=0.012) for III, IV period lung cancer, combined with four kinds of traditional tumor markers measured AUC value was 0.959, with seven kinds of tumor associated antibodies measured AUC value was 0.710, with four traditional tumor markers measured AUC values higher than the combined seven kinds of antibodies, and the difference was statistically Meaning (P=0.001). For III, IV period lung cancer, combined with seven kinds of tumor associated antibodies measured the sensitivity of 56.15%, specificity of 91.60%, will be combined with four kinds of traditional tumor markers in the diagnosis specificity value of 91.60%, the diagnostic sensitivity can reach 90.80%, higher than the sensitivity of combined with seven kinds of antibodies, a the difference was significant (P=0.000). The study concluded that a new group of tumor associated antibodies can be used as a new method for early diagnosis of lung cancer, which has high sensitivity and specificity. Different histological types, non-small cell lung cancer staging, tumor size had no effect on the levels of autoantibodies.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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