自身抗体检测在肺癌诊断与筛查中的作用
发布时间：2018-07-17 21:35
【摘要】：目的:肺癌的发病率和死亡率居高不下。此外一些不健康的饮食生活习惯、外界大气环境的污染、职业粉尘及化学元素的接触等危险因素及烟草行业的流行带给我们的影响,都促成着肺癌的发生与形成,时刻威胁着人类的健康。由于肺癌的恶性程度较高,且在疾病早期缺乏特异性的临床症状,不能够做到早发现、早治疗,从而使得病情延误,大部分患者确诊肺癌时已处于晚期阶段,仅以姑息对症治疗为主,从而大大缩短了生存期。因此,肺癌的诊断,甚至是早期筛查诊断就显得尤为重要,为延长患者生存时间、改善患者生活质量提供了重要前提。病理学诊断仍是诊断肺癌的金标准。低剂量CT是目前主要的肺癌筛查手段,但由于其过高的假阳性率、射线辐射效应、过度诊断及高昂的检查费用等一系列问题,能否使患者真正受益还存在争议。近年来,血清肺癌自身抗体的检测手段在肺癌的诊断与筛查中显示出较好的敏感性和特异性,其简便、无创、便于推广的特点提高了受试者的依从性,为肺癌的诊断与筛查提供了新思路。p53基因突变导致的p53蛋白失活是癌症产生的一个重要步骤。p53自身抗体通常针对发生突变的p53基因产物而产生。PGP9.5是表达在神经组织中的一种泛素水解酶,在原发性肺癌和肺癌细胞系中有大量表达。SOX2是一个转录因子,诱导肿瘤癌信号EGFR及BCL2L1,促进肺癌细胞的增殖、存活。GAGE 7属于肿瘤/睾丸抗原,只表达于恶性肿瘤和睾丸组织,具有抗细胞凋亡活性。GBU4-5属于ATP结合RNA解旋酶,在癌变过程中发挥重要作用,同时有肿瘤特异性和免疫原性。MAGE A1属人黑色素瘤抗原家族,只表达于恶性肿瘤和睾丸组织,可能与基因转录调节和癌症的转化或进展有关。CAGE属于DEAD box解旋酶家族,它的表达量与细胞周期有关,在癌细胞中激活ERK和p38蛋白并增加肿瘤细胞的扩散。本文收集了不同类型患者的血清标本,并应用酶联免疫法(ELISA)分组进行血清七种自身抗体(p53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1、CAGE)水平的检测,观察此检测方法对肺癌诊断与筛查的灵敏度和特异度,并对比组间抗体水平的差异性,探讨肺癌自身抗体检测方法在肺癌诊断与筛查中的作用。方法:纳入2016年11月-2017年2月就诊于河北医科大学第四医院的患者共140例,经病理学检查明确组织分型及TNM分期的肺癌,且排除其它脏器恶性肿瘤者88例,设为肺癌组,经影像学或病理学检查排除肺癌及其它脏器恶性肿瘤者47例(包括良性肺部疾病患者34例,健康受试者13例),设为对照组,经病理证实为血管免疫母性T细胞淋巴瘤患者1例、错构瘤患者2例、畸胎瘤患者1例、肉瘤患者1例。全血采集后经过离心收集血清标本,并对其进行分组、编号,用ELISA方法对血清七种自身抗体进行检测:本实验采用的试剂盒将纯化的七个抗原包被到固相板表面。向包被抗原的微孔中分别加入稀释好的血清样本,经孵育使血清样本中的自身抗体与固相载体上的抗原发生特异性结合。洗掉没有结合的样本,加入酶标记抗人IgG抗体(酶结合物)。第二次孵育使酶标记抗人IgG抗体与吸附到固相载体上的自身抗体结合,形成抗原-抗体-酶标抗体复合物,洗掉没有结合的酶标记抗人IgG抗体,加入显色剂底物反应后用酶标仪在450nm波长下测定其吸光度,通过标准曲线计算出自身抗体的相对浓度,并根据“阳性判断值”对检测的抗体浓度做出“阴性”、“阳性”的结果判断,七种自身抗体的正常上限值如下:p53:13.1U/ml;PGP9.5:11.1U/ml;SOX2:10.3U/ml;GAGE7:14.4U/ml;GBU4-5:7.0U/ml;MAGEA1:11.9U/ml;CAGE:7.2U/ml。(注:本数据经过2008例大样本多中心临床试验验证),从而得出此方法的灵敏度和特异度,并对比组间检测阳性率及组间抗体水平的差异性。非正态计量资料组间差异采用Mann-Whitney U检验。组间检测阳性率的比较采用卡方检验。所有检验都为双侧检验,P0.05为差异具有统计学意义。结果:1研究对象的临床特征肺癌组纳入88例肺癌患者作为研究对象。其中男性患者56例,占63.6%,年龄范围分布在35-80岁,平均年龄为61.2±9.4岁,年龄≥60岁者55例,占62.5%;腺癌患者54例,占61.4%,鳞癌患者18例,占20.4%,其它类型肺癌患者16例,占18.2%;有吸烟史者42例,占47.7%;Ⅰ、Ⅱ期肺癌患者53例,占60.2%,Ⅲ、Ⅳ期肺癌患者35例,占39.8%。良性肺部疾病组纳入34例良性肺部疾病患者作为研究对象。其中男性患者18例,占52.9%;年龄范围分布在25-86岁,平均年龄为54.8±16.2岁,年龄≥60岁者11例,占32.4%;有吸烟史者10例,占29.4%;肺炎患者16例,占47.0%,肺结核患者9例,占26.5%,慢性阻塞性肺疾病患者5例,占14.7%,其它类型患者4例,占11.8%。健康人群组纳入13例健康受试者作为研究对象。其中男性患者6例,占46.2%;年龄范围分布在39-76岁,平均年龄为56.5±11.5岁,年龄≥60岁者4例,占30.8%。另有血管免疫母性T细胞淋巴瘤患者1例、错构瘤患者2例、畸胎瘤患者1例、肉瘤患者1例。2肺癌组与对照组七种自身抗体检测阳性率的比较:肺癌组的p53和GBU4-5抗体检测的阳性率均高于对照组(p53:17.0%vs4.3%,P0.05;GBU4-5:15.9%vs0%,P0.05)。其余五种自身抗体在肺癌组与对照组之间的检测阳性率均无统计学差异(P0.05)。3七种自身抗体单独检测对肺癌筛查的灵敏度、特异度、诊断符合率、正确指数:灵敏度:9.1%-17%;特异度:89.4%-100%;诊断符合率:38.5%-45.2%;正确指数:0.03-0.16。4自身抗体联合检测对肺癌筛查的灵敏度、特异度、诊断符合率、正确指数:p53与GBU4-5抗体联合检测的灵敏度为27.2%,特异度为95.7%,诊断符合率为51.1%,正确指数为0.23;p53、GBU4-5与MAGEA1抗体联合检测的灵敏度为34.1%,特异度为91.5%,诊断符合率为54.1%,正确指数为0.26;七种自身抗体联合检测的灵敏度为46.6%,特异度为70.2%,诊断符合率为54.8%,正确指数为0.17。5七种抗体联合检测对不同类型肺癌筛查的灵敏度及特异度:七种抗体联合检测对肺腺癌诊断的灵敏度为35.2%,特异度为70.2%;对肺鳞癌诊断的灵敏度为72.2%,特异度为70.2%。6肺癌组与对照组七种自身抗体表达水平的比较:肺癌组p53抗体表达水平高于对照组(2.30(0.83,7.18)vs1.60(0.20,2.80),P0.05)。其余六种自身抗体在肺癌组与对照组之间的表达水平无统计学差异(P0.05)。7不同病理类型肺癌与对照组七种自身抗体表达水平的比较:7.1肺腺癌与肺鳞癌患者血清七种自身抗体表达水平的比较:肺鳞癌患者PGP9.5抗体表达水平高于肺腺癌患者(5.05(2.13,19.85)vs2.45(1.60,3.73),P0.05)。其余六种自身抗体在肺腺癌与肺鳞癌患者之间的表达水平均无统计学差异(P0.05)。7.2肺腺癌患者与对照组血清七种自身抗体表达水平的比较:七种自身抗体在肺腺癌患者与对照组之间的表达水平均无统计学差异(P0.05)。7.3肺鳞癌患者与对照组血清七种自身抗体表达水平的比较:肺鳞癌患者血清p53、PGP9.5、MAGEA1抗体的表达水平均高于对照组,差异具有统计学意义(p53:2.95(1.63,19.70)vs1.60(0.20,2.80),P0.05;PGP9.5:5.05(2.13,19.85)vs2.60(1.90,4.00),P0.05;MAGEA1:2.15(0.20,13.58)vs0.50(0.10,1.70),P0.05)。其余四种自身抗体在肺鳞癌患者与对照组之间的表达水平均无统计学差异(P0.05)。8Ⅰ、Ⅱ期肺癌患者与Ⅲ、Ⅳ期肺癌患者血清自身抗体表达水平的比较:Ⅲ、Ⅳ期肺癌患者血清PGP9.5、GBU4-5、CAGE抗体的表达水平均高于Ⅰ、Ⅱ期肺癌患者,差异具有统计学意义(PGP9.5:3.10(2.30,18.10)vs2.30(1.55,3.75),P0.05;GBU4-5:1.50(0.20,22.00)vs0.40(0.00,1.15),P0.05;CAGE:1.70(1.20,8.10)vs1.40(0.20,2.05),P0.05)。其余四种自身抗体在Ⅰ、Ⅱ期与Ⅲ、Ⅳ期患者之间的表达水平均无统计学差异(P0.05)。结论:1单一抗体检测(p53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1、CAGE)对肺癌筛查的特异度较高(89.4%-100%),灵敏度较低(9.1%-17.0%),尚不能满足作为肺癌筛查的指标。2两个(p53与GBU4-5)或三个(p53、GBU4-5与MAGEA1)肺癌自身抗体联合检测较单一抗体检测可以提高检测的灵敏度。3七种血清自身抗体联合检测对肺癌筛查的灵敏度为46.6%,特异度为70.2%,推荐七种自身抗体联合检测技术应用于肺癌的临床筛查工作中。4 p53、PGP9.5、MAGEA1抗体可作为肺鳞癌与良性肺疾病的鉴别指标。5 PGP9.5、GBU4-5、CAGE抗体的表达水平与肿瘤负荷相关。
[Abstract]:Objective: the incidence and mortality of lung cancer are high. In addition, some unhealthy dietary habits, ambient air pollution, occupational dust and chemical elements contact and other dangerous factors, as well as the impact of the tobacco industry, have contributed to the occurrence and formation of lung cancer and threaten human health at all times. Due to lung cancer It has a high degree of malignancy and lack of specific clinical symptoms in the early stage of the disease. It can not be found early, early treatment, so that the disease is delayed, most patients are in the late stage of diagnosis of lung cancer, only with palliative treatment, thus greatly shortening the life period. Therefore, the diagnosis of lung cancer, even early screening and diagnosis, It is particularly important to provide an important prerequisite for prolonging the patient's survival time and improving the quality of life of the patients. The pathological diagnosis is still the gold standard for the diagnosis of lung cancer. Low dose CT is the main screening method for lung cancer at present, but it has a series of problems due to its high false positive rate, radiation effect, diagnosis and high cost of examination. In recent years, the detection of serum lung cancer autoantibodies has shown good sensitivity and specificity in the diagnosis and screening of lung cancer. It is simple, noninvasive and easy to spread, which improves the compliance of the subjects, and provides a new idea for the diagnosis and screening of lung cancer.P53 gene mutation caused by P 53 protein inactivation is an important step in cancer production.P53 autoantibodies usually produce.PGP9.5, a ubiquitin hydrolase expressed in nerve tissue, in response to the mutation of the p53 gene product. In the primary lung cancer and lung cancer cell lines, a large number of.SOX2 are expressed as a transcription factor, inducing cancer signal EGFR and BCL2L1, promoting the tumor cancer signal. The proliferation of lung cancer cells, survival.GAGE 7 belongs to tumor / testicular antigen, only expressed in malignant tumor and testis tissue, with anti apoptotic activity.GBU4-5, which belongs to ATP combined with RNA helicase, plays an important role in the process of carcinogenesis, and there are tumor specific and immunogenic.MAGE A1 human melanoma antigen family, only expressed in malignant swelling. Tumor and testicular tissue may be related to gene transcription regulation and cancer transformation or progression..CAGE belongs to the DEAD box helicase family. Its expression is related to cell cycle, activates ERK and p38 protein in cancer cells and increases the proliferation of tumor cells. This article collected serum specimens of different types of patients and applied enzyme linked immunoassay (ELISA). The serum levels of seven serum autoantibodies (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1, CAGE) were detected in the group. The sensitivity and specificity of this detection method to the diagnosis and screening of lung cancer were observed and the difference of the level of antibody between the groups was compared. The role of the self anti examination method of lung cancer in the diagnosis and screening of lung cancer was discussed. Method: 11 in 2016. In February, -2017, 140 cases were diagnosed at the fourth hospital of Hebei Medical University. The lung cancer was identified by pathological examination and TNM staging, and 88 cases of other malignant tumors were excluded. 47 cases of lung cancer and other organ malignant tumors were excluded by imaging or pathological examination (including 34 patients with benign lung disease, 34 For example, 13 healthy subjects were set as control group, 1 cases of vascular immune maternal T cell lymphoma, 2 cases of angiomyolipoma, 2 cases of hamartoma, 1 cases of teratoma and 1 cases of sarcoma. The serum samples were collected by centrifugation after the whole blood collection, and they were grouped and numbered by ELISA method. The purified seven antigen packages were coated on the surface of the solid phase plate. The diluted serum samples were added to the micropores of the coated antigen, and the autoantibodies in the serum samples were specifically combined with the antigen on the solid carrier. The non binding samples were washed away and the anti human IgG antibody (enzyme binding) was added to the enzyme labelled. The second incubation made the enzyme labeled anti human IgG antibody combined with the autoantibody adsorbed on the solid phase carrier, formed an antigen antibody enzyme antibody complex, washed out the anti human IgG antibody with the non binding enzyme label, and then used the enzyme labeled instrument to determine the absorbance at the 450nm wavelength after adding the chromogenic agent substrate and calculated the autoantibody by the standard curve. Relative concentration, and according to the "positive judgement value" to the antibody concentration of the detected "negative", "positive" results to judge the normal upper limit of the seven kinds of autoantibodies as follows: p53:13.1U/ml; PGP9.5:11.1U/ml; SOX2:10.3U/ml; GAGE7:14.4U/ml; GBU4-5:7.0U/ml; MAGEA1: 11.9U/ml; CAGE:7.2U/ml. (Note: this data passes 2008 large samples more. In the central clinical trial, the sensitivity and specificity of this method were obtained, and the difference between the positive rate and the level of intergroup antibody was compared. The difference between the non normal measurement data groups was tested by Mann-Whitney U test. The comparison of the positive rates between groups was checked by chi square test. All the tests were bilateral test, and P0.05 was a differential system. Results: 1 the clinical features of the lung cancer group were included in 88 cases of lung cancer in 56 cases, accounting for 63.6%, the age range was 35-80 years old, the average age was 61.2 + 9.4 years, the age was 60 years old, 55 cases, 62.5%, 54 cases of adenocarcinoma, 61.4%, squamous carcinoma 18, other types of lung cancer. 16 cases, accounting for 18.2%, 42 cases of smoking history, accounting for 47.7%, 53 cases of lung cancer in stage II, 60.2%, III and stage IV lung cancer in 35 cases, which accounted for 34 cases of benign lung disease in 39.8%. benign lung disease group as the research object. Among them, the male patients were 18 cases, accounting for 52.9%, the age range was 25-86 years old, the average age was 54.8 + 16.2 years, the age was more than 6. There were 11 cases of 0 years old, accounting for 32.4%, 10 cases of smoking history, 16 cases of pneumonia, 47%, 9 cases of pulmonary tuberculosis, 26.5%, 5 cases of chronic obstructive pulmonary disease, 14.7%, and other types of patients, which accounted for the healthy subjects of 11.8%. healthy subjects as research subjects. -76 years old, the average age was 56.5 + 11.5 years old, 4 cases aged more than 60 years old, accounting for 1 cases of 30.8%. and 1 cases of vascular immune maternal T cell lymphoma, 2 cases of hamartomas, 1 cases of teratoma, 1 cases of sarcoma patients with.2 lung cancer and the control group. The positive rate of p53 and GBU4-5 antibody in lung cancer group was higher than that of p53 and GBU4-5 antibody. The control group (p53:17.0%vs4.3%, P0.05; GBU4-5:15.9%vs0%, P0.05). The positive rates of the other five kinds of autoantibodies in the lung cancer group and the control group were not statistically different (P0.05).3 seven autoantibodies for lung cancer screening sensitivity, specificity, diagnostic coincidence rate, correct index: sensitivity: 9.1%-17%; specificity: 89.4%-100%; diagnosis. Fracture coincidence rate: 38.5%-45.2%; correct index: sensitivity, specificity, diagnostic coincidence rate and correct index of 0.03-0.16.4 autoantibody combined detection of lung cancer screening: the sensitivity of combined detection of p53 and GBU4-5 antibody was 27.2%, specificity was 95.7%, diagnostic coincidence rate was 51.1%, correct index was 0.23; p53, GBU4-5 and MAGEA1 antibody were sensitive combined detection. The degree is 34.1%, the specificity is 91.5%, the diagnostic coincidence rate is 54.1%, the correct index is 0.26; the sensitivity of the combined detection of seven kinds of autoantibodies is 46.6%, the specificity is 70.2%, the diagnostic coincidence rate is 54.8%, the correct index is the sensitivity and specificity of the combined detection of 0.17.5 seven antibodies against different types of lung cancer screening. Seven kinds of antibodies are combined to detect the lung gland. The sensitivity of the cancer diagnosis was 35.2%, the specificity was 70.2%, the sensitivity of the diagnosis of lung squamous cell carcinoma was 72.2%, the specificity was the comparison of the expression level of seven kinds of autoantibodies in the 70.2%.6 lung cancer group and the control group: the expression level of p53 antibody in the lung cancer group was higher than that of the control group (2.30 (0.83,7.18) vs1.60 (0.20,2.80), P0.05). The other six kinds of autoantibodies were in the lung cancer group and the control There was no statistical difference between the groups (P0.05) the comparison of the expression levels of seven kinds of autoantibodies in different pathological types of lung cancer and control group: 7.1 comparison of the level of serum seven autoantibodies in 7.1 lung adenocarcinoma and squamous cell carcinoma: the expression level of PGP9.5 antibody in lung squamous cell carcinoma was higher than that of lung adenocarcinoma (5.05 (2.13,19.85) vs2.45 (1.60,3.73), P 0.05) the expression level of the other six kinds of autoantibodies in lung adenocarcinoma and lung squamous cell carcinoma was not statistically significant (P0.05) the comparison of the level of seven kinds of autoantibodies in the patients with.7.2 lung adenocarcinoma and the control group: the level of the seven kinds of autoantibodies in the patients with lung adenocarcinoma and the control group had no statistical difference (P0.05).7.3 lung squamous cell carcinoma The expression level of seven kinds of autoantibodies in the serum of the patients and the control group: the levels of serum p53, PGP9.5 and MAGEA1 antibodies in the patients with lung squamous cell carcinoma were higher than those in the control group, and the difference was statistically significant (p53:2.95 (1.63,19.70) vs1.60 (0.20,2.80), P0.05; PGP9.5:5.05 (2.13,19.85) vs2.60 (1.90,4.00)), P0.05). The expression levels of the other four kinds of autoantibodies in the lung squamous cell carcinoma patients and the control group were not statistically different (P0.05).8 I, stage II lung cancer patients and stage III and IV lung cancer patients' serum autoantibody expression levels: III, stage IV lung cancer patients' serum PGP9.5, GBU4-5, CAGE antibody levels were higher than that of stage I, stage II lung cancer patients, The differences were statistically significant (PGP9.5:3.10 (2.30,18.10) vs2.30 (1.55,3.75), P0.05; GBU4-5:1.50 (0.20,22.00) vs0.40 (0.00,1.15), P0.05; CAGE:1.70 (1.20,8.10)). There was no significant difference in the expression level between the other four kinds of autoantibodies in stage I, stage II and stage IV patients. Conclusion: 1 single antibody detection (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1, CAGE) with higher specificity (89.4%-100%) for lung cancer screening (89.4%-100%) and low sensitivity (9.1%-17.0%), it is not yet able to meet the two (p53 and GBU4-5) or three of the lung cancer screening indicators (p53 and GBU4-5) or the single antibody detection can improve the sensitivity of seven kinds of detection. The sensitivity of combined detection of serum autoantibodies to lung cancer screening is 46.6% and the specificity is 70.2%. Seven kinds of autoantibody combined detection techniques are recommended for the clinical screening of lung cancer,.4 p53, PGP9.5, MAGEA1 antibody can be used as a differential indicator of lung squamous cell carcinoma and benign lung disease.5 PGP9.5, GBU4-5, CAGE antibody expression and tumor load Relevant.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
本文编号：2131008
[Abstract]:Objective: the incidence and mortality of lung cancer are high. In addition, some unhealthy dietary habits, ambient air pollution, occupational dust and chemical elements contact and other dangerous factors, as well as the impact of the tobacco industry, have contributed to the occurrence and formation of lung cancer and threaten human health at all times. Due to lung cancer It has a high degree of malignancy and lack of specific clinical symptoms in the early stage of the disease. It can not be found early, early treatment, so that the disease is delayed, most patients are in the late stage of diagnosis of lung cancer, only with palliative treatment, thus greatly shortening the life period. Therefore, the diagnosis of lung cancer, even early screening and diagnosis, It is particularly important to provide an important prerequisite for prolonging the patient's survival time and improving the quality of life of the patients. The pathological diagnosis is still the gold standard for the diagnosis of lung cancer. Low dose CT is the main screening method for lung cancer at present, but it has a series of problems due to its high false positive rate, radiation effect, diagnosis and high cost of examination. In recent years, the detection of serum lung cancer autoantibodies has shown good sensitivity and specificity in the diagnosis and screening of lung cancer. It is simple, noninvasive and easy to spread, which improves the compliance of the subjects, and provides a new idea for the diagnosis and screening of lung cancer.P53 gene mutation caused by P 53 protein inactivation is an important step in cancer production.P53 autoantibodies usually produce.PGP9.5, a ubiquitin hydrolase expressed in nerve tissue, in response to the mutation of the p53 gene product. In the primary lung cancer and lung cancer cell lines, a large number of.SOX2 are expressed as a transcription factor, inducing cancer signal EGFR and BCL2L1, promoting the tumor cancer signal. The proliferation of lung cancer cells, survival.GAGE 7 belongs to tumor / testicular antigen, only expressed in malignant tumor and testis tissue, with anti apoptotic activity.GBU4-5, which belongs to ATP combined with RNA helicase, plays an important role in the process of carcinogenesis, and there are tumor specific and immunogenic.MAGE A1 human melanoma antigen family, only expressed in malignant swelling. Tumor and testicular tissue may be related to gene transcription regulation and cancer transformation or progression..CAGE belongs to the DEAD box helicase family. Its expression is related to cell cycle, activates ERK and p38 protein in cancer cells and increases the proliferation of tumor cells. This article collected serum specimens of different types of patients and applied enzyme linked immunoassay (ELISA). The serum levels of seven serum autoantibodies (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1, CAGE) were detected in the group. The sensitivity and specificity of this detection method to the diagnosis and screening of lung cancer were observed and the difference of the level of antibody between the groups was compared. The role of the self anti examination method of lung cancer in the diagnosis and screening of lung cancer was discussed. Method: 11 in 2016. In February, -2017, 140 cases were diagnosed at the fourth hospital of Hebei Medical University. The lung cancer was identified by pathological examination and TNM staging, and 88 cases of other malignant tumors were excluded. 47 cases of lung cancer and other organ malignant tumors were excluded by imaging or pathological examination (including 34 patients with benign lung disease, 34 For example, 13 healthy subjects were set as control group, 1 cases of vascular immune maternal T cell lymphoma, 2 cases of angiomyolipoma, 2 cases of hamartoma, 1 cases of teratoma and 1 cases of sarcoma. The serum samples were collected by centrifugation after the whole blood collection, and they were grouped and numbered by ELISA method. The purified seven antigen packages were coated on the surface of the solid phase plate. The diluted serum samples were added to the micropores of the coated antigen, and the autoantibodies in the serum samples were specifically combined with the antigen on the solid carrier. The non binding samples were washed away and the anti human IgG antibody (enzyme binding) was added to the enzyme labelled. The second incubation made the enzyme labeled anti human IgG antibody combined with the autoantibody adsorbed on the solid phase carrier, formed an antigen antibody enzyme antibody complex, washed out the anti human IgG antibody with the non binding enzyme label, and then used the enzyme labeled instrument to determine the absorbance at the 450nm wavelength after adding the chromogenic agent substrate and calculated the autoantibody by the standard curve. Relative concentration, and according to the "positive judgement value" to the antibody concentration of the detected "negative", "positive" results to judge the normal upper limit of the seven kinds of autoantibodies as follows: p53:13.1U/ml; PGP9.5:11.1U/ml; SOX2:10.3U/ml; GAGE7:14.4U/ml; GBU4-5:7.0U/ml; MAGEA1: 11.9U/ml; CAGE:7.2U/ml. (Note: this data passes 2008 large samples more. In the central clinical trial, the sensitivity and specificity of this method were obtained, and the difference between the positive rate and the level of intergroup antibody was compared. The difference between the non normal measurement data groups was tested by Mann-Whitney U test. The comparison of the positive rates between groups was checked by chi square test. All the tests were bilateral test, and P0.05 was a differential system. Results: 1 the clinical features of the lung cancer group were included in 88 cases of lung cancer in 56 cases, accounting for 63.6%, the age range was 35-80 years old, the average age was 61.2 + 9.4 years, the age was 60 years old, 55 cases, 62.5%, 54 cases of adenocarcinoma, 61.4%, squamous carcinoma 18, other types of lung cancer. 16 cases, accounting for 18.2%, 42 cases of smoking history, accounting for 47.7%, 53 cases of lung cancer in stage II, 60.2%, III and stage IV lung cancer in 35 cases, which accounted for 34 cases of benign lung disease in 39.8%. benign lung disease group as the research object. Among them, the male patients were 18 cases, accounting for 52.9%, the age range was 25-86 years old, the average age was 54.8 + 16.2 years, the age was more than 6. There were 11 cases of 0 years old, accounting for 32.4%, 10 cases of smoking history, 16 cases of pneumonia, 47%, 9 cases of pulmonary tuberculosis, 26.5%, 5 cases of chronic obstructive pulmonary disease, 14.7%, and other types of patients, which accounted for the healthy subjects of 11.8%. healthy subjects as research subjects. -76 years old, the average age was 56.5 + 11.5 years old, 4 cases aged more than 60 years old, accounting for 1 cases of 30.8%. and 1 cases of vascular immune maternal T cell lymphoma, 2 cases of hamartomas, 1 cases of teratoma, 1 cases of sarcoma patients with.2 lung cancer and the control group. The positive rate of p53 and GBU4-5 antibody in lung cancer group was higher than that of p53 and GBU4-5 antibody. The control group (p53:17.0%vs4.3%, P0.05; GBU4-5:15.9%vs0%, P0.05). The positive rates of the other five kinds of autoantibodies in the lung cancer group and the control group were not statistically different (P0.05).3 seven autoantibodies for lung cancer screening sensitivity, specificity, diagnostic coincidence rate, correct index: sensitivity: 9.1%-17%; specificity: 89.4%-100%; diagnosis. Fracture coincidence rate: 38.5%-45.2%; correct index: sensitivity, specificity, diagnostic coincidence rate and correct index of 0.03-0.16.4 autoantibody combined detection of lung cancer screening: the sensitivity of combined detection of p53 and GBU4-5 antibody was 27.2%, specificity was 95.7%, diagnostic coincidence rate was 51.1%, correct index was 0.23; p53, GBU4-5 and MAGEA1 antibody were sensitive combined detection. The degree is 34.1%, the specificity is 91.5%, the diagnostic coincidence rate is 54.1%, the correct index is 0.26; the sensitivity of the combined detection of seven kinds of autoantibodies is 46.6%, the specificity is 70.2%, the diagnostic coincidence rate is 54.8%, the correct index is the sensitivity and specificity of the combined detection of 0.17.5 seven antibodies against different types of lung cancer screening. Seven kinds of antibodies are combined to detect the lung gland. The sensitivity of the cancer diagnosis was 35.2%, the specificity was 70.2%, the sensitivity of the diagnosis of lung squamous cell carcinoma was 72.2%, the specificity was the comparison of the expression level of seven kinds of autoantibodies in the 70.2%.6 lung cancer group and the control group: the expression level of p53 antibody in the lung cancer group was higher than that of the control group (2.30 (0.83,7.18) vs1.60 (0.20,2.80), P0.05). The other six kinds of autoantibodies were in the lung cancer group and the control There was no statistical difference between the groups (P0.05) the comparison of the expression levels of seven kinds of autoantibodies in different pathological types of lung cancer and control group: 7.1 comparison of the level of serum seven autoantibodies in 7.1 lung adenocarcinoma and squamous cell carcinoma: the expression level of PGP9.5 antibody in lung squamous cell carcinoma was higher than that of lung adenocarcinoma (5.05 (2.13,19.85) vs2.45 (1.60,3.73), P 0.05) the expression level of the other six kinds of autoantibodies in lung adenocarcinoma and lung squamous cell carcinoma was not statistically significant (P0.05) the comparison of the level of seven kinds of autoantibodies in the patients with.7.2 lung adenocarcinoma and the control group: the level of the seven kinds of autoantibodies in the patients with lung adenocarcinoma and the control group had no statistical difference (P0.05).7.3 lung squamous cell carcinoma The expression level of seven kinds of autoantibodies in the serum of the patients and the control group: the levels of serum p53, PGP9.5 and MAGEA1 antibodies in the patients with lung squamous cell carcinoma were higher than those in the control group, and the difference was statistically significant (p53:2.95 (1.63,19.70) vs1.60 (0.20,2.80), P0.05; PGP9.5:5.05 (2.13,19.85) vs2.60 (1.90,4.00)), P0.05). The expression levels of the other four kinds of autoantibodies in the lung squamous cell carcinoma patients and the control group were not statistically different (P0.05).8 I, stage II lung cancer patients and stage III and IV lung cancer patients' serum autoantibody expression levels: III, stage IV lung cancer patients' serum PGP9.5, GBU4-5, CAGE antibody levels were higher than that of stage I, stage II lung cancer patients, The differences were statistically significant (PGP9.5:3.10 (2.30,18.10) vs2.30 (1.55,3.75), P0.05; GBU4-5:1.50 (0.20,22.00) vs0.40 (0.00,1.15), P0.05; CAGE:1.70 (1.20,8.10)). There was no significant difference in the expression level between the other four kinds of autoantibodies in stage I, stage II and stage IV patients. Conclusion: 1 single antibody detection (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1, CAGE) with higher specificity (89.4%-100%) for lung cancer screening (89.4%-100%) and low sensitivity (9.1%-17.0%), it is not yet able to meet the two (p53 and GBU4-5) or three of the lung cancer screening indicators (p53 and GBU4-5) or the single antibody detection can improve the sensitivity of seven kinds of detection. The sensitivity of combined detection of serum autoantibodies to lung cancer screening is 46.6% and the specificity is 70.2%. Seven kinds of autoantibody combined detection techniques are recommended for the clinical screening of lung cancer,.4 p53, PGP9.5, MAGEA1 antibody can be used as a differential indicator of lung squamous cell carcinoma and benign lung disease.5 PGP9.5, GBU4-5, CAGE antibody expression and tumor load Relevant.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
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