發(fā)布時(shí)間：2018-05-01 01:12

  本文選題：肺癌標(biāo)志物 + BALF�。� 參考：《第三軍醫(yī)大學(xué)》2016年碩士論文

【摘要】：背景:目前全球發(fā)病率、病死率最高的惡性腫瘤是肺癌,目前分為非小細(xì)胞肺癌(nonsmall-cell lung cancer,NSCLC)和小細(xì)胞肺癌(Small Cell Lung Cancer,SCLC),NSCLC以腺癌和鱗癌兩種病理組織類型最多見(jiàn)。腫瘤標(biāo)志物為目前常用的腫瘤輔助診斷方法,目前檢測(cè)腫瘤標(biāo)志物,主要是血清或血漿標(biāo)本。如果對(duì)肺泡灌洗液(bronchoaiveoiar Lavage Fluid,BALF)更靠近肺癌組織的標(biāo)本進(jìn)行檢測(cè),可能會(huì)獲得更好的受試者曲線(receiver operating characteristic curve,ROC曲線)面積。同時(shí),腫瘤標(biāo)志物的升高、降低及變化,對(duì)腫瘤患者的預(yù)后、轉(zhuǎn)移甚至耐藥也是有一定的提示作用的,這主要是由于腫瘤標(biāo)志物與腫瘤的生物活性息息相關(guān)。由于本文的研究對(duì)象為單純肺癌患者,故也可稱之為肺癌標(biāo)志物。本文擬對(duì)尿二乙酰精氨(Urine di-acetyl sperimine,Di Ac Spm)、腫瘤釋放蛋白(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)、神經(jīng)元特異性烯醇化酶(neuron-specific enolase,NSE)、細(xì)胞角蛋白19片段(Cytokerantin-19-fragment,CYFRA21-1)7種肺癌標(biāo)志物進(jìn)行研究,以期發(fā)現(xiàn)其在肺癌診斷、轉(zhuǎn)移、耐藥及預(yù)后中的臨床意義。方法:1.采用酶聯(lián)免疫法對(duì)40例肺癌患者及40例肺部良性病變患者的BALF及血清進(jìn)行腫瘤標(biāo)志物濃度的檢測(cè),采用合適的統(tǒng)計(jì)學(xué)方法比較差異性;計(jì)算ROC曲線下面積及診斷敏感性、特異性;分析其濃度與肺癌分型(腺癌、鱗癌)、肺癌基線長(zhǎng)度、遠(yuǎn)處轉(zhuǎn)移靶器官數(shù)目及TNM分期是否有相關(guān)性。2.35名肺癌化療患者包括完全緩解(complete response,CR)0人,部分緩解(partial response,PR)15人,疾病穩(wěn)定(stable disease,SD)13人,疾病進(jìn)展(progressive disease,PD)7人。將其分為化療有效組(CR+PR+SD)及化療無(wú)效組(PD),采用非參數(shù)檢驗(yàn)法分別分析在BALF及血清中,兩組間7種肺癌標(biāo)志物的濃度是否具有差異性并隨訪PD組病人下一步治療情況。3.對(duì)33例晚期NSCLC患者(IIIB及IV期)進(jìn)行為期2年的隨訪,對(duì)2年內(nèi)死亡的相關(guān)危險(xiǎn)因素進(jìn)行Logistic回歸分析。結(jié)果:1.根據(jù)單因素方差分析,肺部良性疾病組BALF中Di Ac Spm、TLP、pro-SFTPB、CEA的濃度顯著低于肺癌組(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。肺部良性病變組血清中TLP、pro-SFTPB及CEA的濃度顯著低于肺癌組(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.僅BALF中TLP、CEA的濃度與腫瘤基線長(zhǎng)度、血清中pro-SFTPB的濃度與靶器官轉(zhuǎn)移數(shù)目有正相關(guān)性(Spearman相關(guān)系數(shù)分別為0.353,0.274和0.312),P0.05,其余組與腫瘤基線長(zhǎng)度、靶器官轉(zhuǎn)移數(shù)量無(wú)相關(guān)性,P0.05;7種腫瘤標(biāo)志物在兩種標(biāo)本中濃度與肺癌分型(鱗癌、腺癌)、TNM分期均無(wú)相關(guān)性,P0.05。3.肺癌標(biāo)志物在BALF標(biāo)本中的曲線下面積大于血清標(biāo)本。4.Di Ac Spm、TLP、pro-SFTPB這3種新的肺癌標(biāo)志物在BALF及血清中的ROC曲線下面積大于NSE,與CEA很接近。5.根據(jù)非參數(shù)檢驗(yàn),肺腺癌“紫杉醇+奈達(dá)鉑”化療患者中,化療有效組血清中pro-SFTPB的濃度顯著高于化療無(wú)效組(中位數(shù)分別為47.22 vs 29.67 ng/m L),P0.05。6.經(jīng)單因素回歸分析,“化療后Di Ac Spm、UCHL1、CEA血清濃度未降低”;“并發(fā)上腔靜脈綜合征(superior vena cava syndrome,SVCS)患者”;“未堅(jiān)持規(guī)范治療患者”為晚期NSCLC患者2年死亡危險(xiǎn)因素。7.經(jīng)多因素回歸分析,“化療后Di Ac Spm血清濃度未降低”及“并發(fā)SVCS”為晚期的NSCLC患者2年內(nèi)死亡的危險(xiǎn)因素。結(jié)論:1.本文中,Di Ac Spm、TLP、pro-SFTPB這3種肺癌標(biāo)志物在BALF及血清標(biāo)雙份本中的曲線下面積接近于經(jīng)典標(biāo)志物CEA,對(duì)肺癌的診斷有一定的價(jià)值。2.本文中,所有肺癌標(biāo)志物在BALF標(biāo)本中的曲線下面積大于血清標(biāo)本。3.TLP、CEA在BALF中的濃度與腫瘤基線長(zhǎng)度、pro-SFTPB在血清中的濃度與靶器官轉(zhuǎn)移數(shù)目有正相關(guān)性。4.血清中pro-SFTPB的濃度降低可能提示“紫杉醇+奈達(dá)鉑”耐藥。5.“化療后Di Ac Spm、UCHL1、CEA血清濃度未降低”;“并發(fā)SVCS患者”可能提示預(yù)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.

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R734.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 桑純利;劉向群;吳曉進(jìn);陳云峰;;肺癌患者肺泡灌洗液中Survivin mRNA表達(dá)及其與吸煙相關(guān)性的臨床研究[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2013年24期

2 張鈺;唐亮;毛e，

本文編號(hào)：1827057