TLP等7种肺癌标志物在NSCLC诊断等临床意义的研究

发布时间：2018-05-01 01:12

本文选题：肺癌标志物 + BALF　；参考：《第三军医大学》2016年硕士论文

【摘要】：背景:目前全球发病率、病死率最高的恶性肿瘤是肺癌,目前分为非小细胞肺癌(nonsmall-cell lung cancer,NSCLC)和小细胞肺癌(Small Cell Lung Cancer,SCLC),NSCLC以腺癌和鳞癌两种病理组织类型最多见。肿瘤标志物为目前常用的肿瘤辅助诊断方法,目前检测肿瘤标志物,主要是血清或血浆标本。如果对肺泡灌洗液(bronchoaiveoiar Lavage Fluid,BALF)更靠近肺癌组织的标本进行检测,可能会获得更好的受试者曲线(receiver operating characteristic curve,ROC曲线)面积。同时,肿瘤标志物的升高、降低及变化,对肿瘤患者的预后、转移甚至耐药也是有一定的提示作用的,这主要是由于肿瘤标志物与肿瘤的生物活性息息相关。由于本文的研究对象为单纯肺癌患者,故也可称之为肺癌标志物。本文拟对尿二乙酰精氨(Urine di-acetyl sperimine,Di Ac Spm)、肿瘤释放蛋白(Tumor liberated protein,TLP)、血液前表面活性蛋白(pro-surfactant protein B,pro-SFTPB)、泛素羧基末端水解酶同工酶L1(Ubiquitin-protein hydrolase1,UCHL1)、癌胚抗原(carcino-embryonic antigen,CEA)、神经元特异性烯醇化酶(neuron-specific enolase,NSE)、细胞角蛋白19片段(Cytokerantin-19-fragment,CYFRA21-1)7种肺癌标志物进行研究,以期发现其在肺癌诊断、转移、耐药及预后中的临床意义。方法:1.采用酶联免疫法对40例肺癌患者及40例肺部良性病变患者的BALF及血清进行肿瘤标志物浓度的检测,采用合适的统计学方法比较差异性;计算ROC曲线下面积及诊断敏感性、特异性;分析其浓度与肺癌分型(腺癌、鳞癌)、肺癌基线长度、远处转移靶器官数目及TNM分期是否有相关性。2.35名肺癌化疗患者包括完全缓解(complete response,CR)0人,部分缓解(partial response,PR)15人,疾病稳定(stable disease,SD)13人,疾病进展(progressive disease,PD)7人。将其分为化疗有效组(CR+PR+SD)及化疗无效组(PD),采用非参数检验法分别分析在BALF及血清中,两组间7种肺癌标志物的浓度是否具有差异性并随访PD组病人下一步治疗情况。3.对33例晚期NSCLC患者(IIIB及IV期)进行为期2年的随访,对2年内死亡的相关危险因素进行Logistic回归分析。结果:1.根据单因素方差分析,肺部良性疾病组BALF中Di Ac Spm、TLP、pro-SFTPB、CEA的浓度显著低于肺癌组(Di Ac Spm15.49±6.65 vs 11.67±8.33;TLP 26.26±13.24 vs18.41±12.36;pro-SFTPB 28.30±18.69 vs 19.05±8.93;CEA17.59±7.18 vs 13.91±7.99ng/m L),P0.05。肺部良性病变组血清中TLP、pro-SFTPB及CEA的浓度显著低于肺癌组(TLP33.56±16.72 vs 26.04±15.58,pro-SFTPB43.34±17.33 vs 33.86±33.86;CEA17.16±7.48 vs 13.86±7.81 ng/m L),P0.05。2.仅BALF中TLP、CEA的浓度与肿瘤基线长度、血清中pro-SFTPB的浓度与靶器官转移数目有正相关性(Spearman相关系数分别为0.353,0.274和0.312),P0.05,其余组与肿瘤基线长度、靶器官转移数量无相关性,P0.05;7种肿瘤标志物在两种标本中浓度与肺癌分型(鳞癌、腺癌)、TNM分期均无相关性,P0.05。3.肺癌标志物在BALF标本中的曲线下面积大于血清标本。4.Di Ac Spm、TLP、pro-SFTPB这3种新的肺癌标志物在BALF及血清中的ROC曲线下面积大于NSE,与CEA很接近。5.根据非参数检验,肺腺癌“紫杉醇+奈达铂”化疗患者中,化疗有效组血清中pro-SFTPB的浓度显著高于化疗无效组(中位数分别为47.22 vs 29.67 ng/m L),P0.05。6.经单因素回归分析,“化疗后Di Ac Spm、UCHL1、CEA血清浓度未降低”;“并发上腔静脉综合征(superior vena cava syndrome,SVCS)患者”;“未坚持规范治疗患者”为晚期NSCLC患者2年死亡危险因素。7.经多因素回归分析,“化疗后Di Ac Spm血清浓度未降低”及“并发SVCS”为晚期的NSCLC患者2年内死亡的危险因素。结论:1.本文中,Di Ac Spm、TLP、pro-SFTPB这3种肺癌标志物在BALF及血清标双份本中的曲线下面积接近于经典标志物CEA,对肺癌的诊断有一定的价值。2.本文中,所有肺癌标志物在BALF标本中的曲线下面积大于血清标本。3.TLP、CEA在BALF中的浓度与肿瘤基线长度、pro-SFTPB在血清中的浓度与靶器官转移数目有正相关性。4.血清中pro-SFTPB的浓度降低可能提示“紫杉醇+奈达铂”耐药。5.“化疗后Di Ac Spm、UCHL1、CEA血清浓度未降低”;“并发SVCS患者”可能提示预后不良
[Abstract]:Background: at present the global incidence of the highest incidence of malignant tumor is lung cancer, which is currently divided into non small cell lung cancer (nonsmall-cell lung cancer, NSCLC) and small cell lung cancer (Small Cell Lung Cancer, SCLC). NSCLC is the most common pathological tissue type of adenocarcinoma and squamous cell carcinoma. Tumor markers are commonly used tumor assisted diagnosis methods at present. Before detection of tumor markers, mainly serum or plasma specimens. If bronchoaiveoiar Lavage Fluid (BALF) is closer to the specimens of lung cancer tissue, a better receiver curve (receiver operating characteristic curve, ROC curve) area may be obtained. At the same time, the elevation, decrease and change of tumor markers are increased. It is also suggestive of the prognosis, metastasis and even drug resistance of the cancer patients. This is mainly due to the relationship between tumor markers and the biological activity of the tumor. Because the object of this study is simple lung cancer patients, it can also be called a marker of lung cancer. This article is proposed to Urine di-acetyl sperimine, Di Ac Sp M), tumor release protein (Tumor liberated protein, TLP), pro-surfactant protein B, pro-SFTPB, ubiquitin carboxyl terminal hydrolase isozyme L1, carcinoembryonic antigen, neuron specific enolase. The clinical significance of 7 lung cancer markers, Cytokerantin-19-fragment (Cytokerantin-19-fragment, CYFRA21-1), in the diagnosis, metastasis, resistance and prognosis of lung cancer. Method: 1. using ELISA to detect the concentration of tumor markers in the BALF and serum of 40 patients with lung cancer and 40 cases of benign pulmonary disease. Compare the differences with the appropriate statistical methods; calculate the area under the ROC curve and the sensitivity and specificity of diagnosis; analyze the correlation between the concentration and lung cancer type (adenocarcinoma, squamous cell carcinoma), the length of the lung cancer baseline, the number of distant metastatic target organs and the TNM staging; 0 patients with lung cancer chemotherapy, including complete remission (complete response, CR), are partially delayed. Partial response (PR), 15 people, 13 people with disease stability (stable disease, SD), and 7 people with disease progression (progressive disease, PD). They were divided into effective chemotherapy group (CR+PR+SD) and chemotherapy ineffective group (PD). The difference of the concentration of 7 lung cancer markers between the two groups was analyzed by nonparametric test in the BALF and serum, and the follow-up group was followed up. 33 patients with advanced NSCLC (IIIB and IV) were followed up for 2 years, and the risk factors of death within 2 years were analyzed by Logistic regression analysis. Results: 1. according to the single factor analysis of variance, Di Ac Spm, TLP, pro-SFTPB, and CEA were significantly lower than the lung cancer group in the benign lung disease group BALF. Vs 11.67 + 8.33; TLP 26.26 + 13.24 vs18.41 + 12.36; pro-SFTPB 28.30 + 18.69 vs 19.05 + 8.93; CEA17.59 + 7.18 vs 13.91 + 7.99ng/m L), TLP in the serum of P0.05. lung benign lesion group, which was significantly lower than that of lung cancer group. .86 + 7.81 ng/m L), P0.05.2. only BALF in TLP, TLP, CEA concentration and tumor baseline length, serum pro-SFTPB concentration and target organ transfer number is positive correlation (Spearman correlation coefficient is 0.353,0.274 and 0.312), P0.05, the rest of the tumor baseline length, the number of target organ metastasis is not related, P0.05; 7 kinds of tumor markers in two standard There was no correlation between the concentration and the TNM stage of the lung cancer type (squamous cell carcinoma, adenocarcinoma) and TNM. The area of the P0.05.3. lung cancer markers in the BALF specimens was larger than the serum samples.4.Di Ac Spm, TLP, pro-SFTPB, and the ROC curves in BALF and serum were larger than NSE. In patients with paclitaxel + nedaplatin chemotherapy, the serum concentration of pro-SFTPB in the chemotherapy group was significantly higher than that in the ineffective chemotherapy group (median 47.22 vs 29.67 ng/m L, respectively). P0.05.6. was analyzed by single factor regression, "Di Ac Spm, UCHL1, CEA serum concentration was not reduced after chemotherapy"; "concurrent superior vena cava syndrome (superior vena) CS patients ";" patients who did not adhere to standardized treatment "were risk factors for the 2 year death of late NSCLC patients.7. by multiple factor regression analysis," Di Ac Spm serum concentration after chemotherapy "and" concurrent SVCS "as a risk factor for death within 2 years of late NSCLC patients. Conclusion: 1., Di Ac Spm, TLP, and these 3 lung cancer markers are in the 1. article The area under the curve of the BALF and the two copies of the serum is close to the classic marker CEA. The diagnosis of lung cancer is of certain value. In this paper, the area of all lung cancer markers in the BALF specimen is larger than that of the serum samples.3.TLP, the concentration of CEA in BALF and the length of the tumor baseline, the concentration of pro-SFTPB in the serum and the number of target organ transfer. The decrease of pro-SFTPB in serum of positive correlation.4. may suggest that "paclitaxel + nedaplatin" resistant.5. "Di Ac Spm after chemotherapy, UCHL1, CEA serum concentration is not reduced"; "concurrent SVCS patients" may suggest poor prognosis.

【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R734.2

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