本文選題：腫瘤相關抗體　切入點：肺癌　出處：《大連醫(yī)科大學》2017年碩士論文

【摘要】：研究目的本文探究一組新腫瘤相關抗體(包括p53,NY-ESO-1,CAGE,GBU4-5,SOX2,Hu D,及MAGEA1抗體)對肺癌早期診斷的意義。同時討論分析患者相關臨床因素對自身抗體水平有無影響。研究方法選取2015年11月至2016年4月期間在大連醫(yī)科大學附屬二院因咳嗽、咯血、胸悶等癥狀或因體格檢查行多排螺旋CT,同時對肺內(nèi)病灶行手術切除或取活檢后行病理確認的患者。根據(jù)患者多排螺旋CT結果有無病灶及病灶病理結果,確定為肺癌組(n=397),良性病灶組(n=45)及健康對照組(n=74)。應用酶聯(lián)免疫吸附測定法,分別測定三組樣本血清中七種抗體水平,同時收集三組樣本四種傳統(tǒng)腫瘤標志物水平(包括CEA、SCC、CYFRA211、NSE)。七個腫瘤相關抗體中只要任意一個大于它的臨界值,即認定該患者腫瘤相關抗體組合為陽性。四個傳統(tǒng)腫瘤標志物中只要任意一個大于它的臨界值,即認定該患者傳統(tǒng)腫瘤標志物組合為陽性。分別比較單個抗體與聯(lián)合七種腫瘤相關抗體對于肺癌診斷的敏感性、特異性;分析肺癌患者不同臨床資料(病理類型、TNM分期、病灶大小)對抗體水平有無影響。同時比較聯(lián)合七種腫瘤相關抗體與聯(lián)合四種傳統(tǒng)腫瘤標志物對于不同TNM分期非小細胞肺癌診斷的敏感性、特異性。研究結果1.在肺癌組,聯(lián)合七種腫瘤相關抗體所測定出的陽性率(56.53%)顯著高于良性病灶組(11.11%)及健康對照組(6.76%),差異有統(tǒng)計學意義(c(17)=83.681,P=0.000);且在肺癌組,聯(lián)合七種腫瘤相關抗體所測定出的陽性率明顯較單個抗體陽性率高,差異均有統(tǒng)計學意義(P均0.05)。聯(lián)合七種腫瘤相關抗體得出的診斷特異性為91.60%。該組抗體對肺癌患者的陽性預測值較高,為95.80%;同時陰性預測值為45.42%。2.聯(lián)合七種腫瘤相關抗體得出的診斷特異性為91.60%。當結合健康對照組的CT結果后,診斷的特異性可以進一步提高到95.80%。3.在不同病理類型肺癌間,聯(lián)合七種腫瘤相關抗體所測得的陽性值差異無統(tǒng)計學意義(P=0.507)。對于非小細胞肺癌,聯(lián)合七種腫瘤相關抗體檢測,I期患者陽性率56.39%,II期為57.14%,III期為55.81%,IV為56.32%,不同病程分期患者之間聯(lián)合七種腫瘤相關抗體所測的陽性率差異亦無統(tǒng)計學意義(P=0.999)。對于小細胞肺癌,聯(lián)合七種腫瘤相關抗體檢測,小細胞肺癌擴散期的陽性率(72.00%)顯著高于小細胞肺癌局限期患者(40.91%),差異有統(tǒng)計學差異(c2=4.627,P=0.031)。同時在不同病灶大小肺癌患者之間,聯(lián)合七種腫瘤相關抗體檢測,≤8mm患者陽性率56.67%,8-20mm為55.13%,20-30mm為52.46%,≥30mm為57.89%,超過一個病灶的患者為61.29%,雖然大于30mm病灶陽性率高于小于8mm的病灶,但陽性率的差異無統(tǒng)計學意義(P=0.928)。4.使用ROC曲線分析聯(lián)合七種腫瘤相關抗體及聯(lián)合四種傳統(tǒng)腫瘤標志物檢測對于不同分期非小細胞肺癌診斷的敏感性、特異性、AUC值,對于I、II期非小細胞肺癌,聯(lián)合四種傳統(tǒng)腫瘤標志物所得出的AUC值為0.799,聯(lián)合七種腫瘤相關抗體所得出的AUC值為0.746,AUC值的差異無統(tǒng)計學意義(P0.05)。對于I、II期非小細胞肺癌,聯(lián)合七種腫瘤相關抗體測得診斷敏感性為56.57%,特異性91.60%,將聯(lián)合四種傳統(tǒng)腫瘤標志物所測得的診斷特異性取值為91.60%時,其診斷敏感性只有33.10%,敏感性低于聯(lián)合七種腫瘤相關抗體,且差異有統(tǒng)計學意義(P=0.012)。對于III、IV期肺癌,聯(lián)合四種傳統(tǒng)腫瘤標志物測得的AUC值為0.959,聯(lián)合七種腫瘤相關抗體測得的AUC值為0.710,聯(lián)合四種傳統(tǒng)腫瘤標志物測得的AUC值高于聯(lián)合七種抗體,且差異有統(tǒng)計學意義(P=0.001)。對于III、IV期肺癌,聯(lián)合七種腫瘤相關抗體所測得的敏感性為56.15%,為特異性91.60%,將聯(lián)合四種傳統(tǒng)腫瘤標志物的診斷特異性取值為91.60%時,其診斷的敏感性可到達90.80%,敏感性高于聯(lián)合七種抗體,且差異有統(tǒng)計學意義(P=0.000)。研究結論認為一組新腫瘤相關抗體可以作為早期肺癌診斷一種新方法,其具有較高的敏感性及特異性。不同組織學類型、非小細胞肺癌病程分期、病灶大小對自身抗體水平無影響。
[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.

【學位授予單位】：大連醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2

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