本文選題：肺癌 + 黑色素瘤抗原-As�。� 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：癌癥是人類(lèi)面臨的一個(gè)嚴(yán)重的健康安全問(wèn)題。目前,癌癥死亡率高的有肺癌、結(jié)直腸癌、前列腺癌以及乳腺癌,這4種癌癥幾乎占所有癌癥死亡人數(shù)的一半。在全球癌癥死亡者中肺癌的新增死亡率居高不下。隨著醫(yī)學(xué)科學(xué)水平的發(fā)展,免疫治療由于其創(chuàng)傷小且針對(duì)性強(qiáng)等優(yōu)勢(shì),已成為繼手術(shù)切除治療以及放化療后的一種新的腫瘤治療方式。而尋找高效且特異的靶抗原是腫瘤免疫治療的關(guān)鍵。癌/睪丸抗原(Cancer/testis antigens,CTA)在正常組織中限制性表達(dá)于睪丸組織,偶爾表達(dá)于卵巢和胎盤(pán)組織,在各種腫瘤組織中有不程度表達(dá),具有特異的表達(dá)模式,因此,具有作為腫瘤免疫治療特異靶點(diǎn)的潛在優(yōu)勢(shì)。近年來(lái),本課題組一直重點(diǎn)探索不同腫瘤組織中黑色素瘤相關(guān)抗原(melanoma antigen,MAGE)-A家族的表達(dá)、生物學(xué)功能及作為免疫治療靶點(diǎn)的可行性研究。本研究利用免疫組織化學(xué)染色法以及熒光原位雜交技術(shù)(fluorescent in situ hybridization,FISH)檢測(cè)非小細(xì)胞肺癌(non-small-cell lung cancer,NSCLC)腫瘤組織及其癌旁組織中MAGE-As(包括MAGE-A1、-A2、-A3、-A4、-A6、-A10和A12)的表達(dá)、EGFR基因擴(kuò)增和ALK基因重排情況以及與臨床生物學(xué)指標(biāo)的關(guān)系。進(jìn)一步探討了肺癌患者外周血中MAGE-As基因的表達(dá)與臨床預(yù)后之間的關(guān)系。主要研究?jī)?nèi)容和結(jié)果如下:第一部分非小細(xì)胞肺癌患者腫瘤組織中MAGE-As的表達(dá)及其臨床意義目的:探討黑色素瘤相關(guān)抗原(melanoma antigen,MAGE)-As在非小細(xì)胞肺癌腫瘤組織中的表達(dá),并分析其與患者臨床病理學(xué)特征及其預(yù)后的關(guān)系。方法:1購(gòu)買(mǎi)上海國(guó)家工程研究中心的NSCLC腫瘤組織及相應(yīng)癌旁組織生物芯片各90例,應(yīng)用免疫組織化學(xué)染色法檢測(cè)NSCLC腫瘤組織及相應(yīng)癌旁組織中MAGE-As蛋白的表達(dá)。2利用熒光原位雜交技術(shù)檢測(cè)NSCLC腫瘤組織中EGFR基因擴(kuò)增和ALK基因重排的情況,并分析MAGE-As表達(dá)與EGFR基因擴(kuò)增和ALK基因重排之間的關(guān)系。結(jié)果:1 NSCLC腫瘤組織中MAGE-As蛋白的陽(yáng)性表達(dá)率為45.56%(41/90)。2 MAGE-As蛋白的表達(dá)與患者的臨床病理學(xué)特征、EGFR基因擴(kuò)增和ALK基因重排均無(wú)相關(guān)性(P0.05)。3 Log-Rank檢驗(yàn)顯示,MAGE-As蛋白表達(dá)陽(yáng)性的NSCLC患者的生存期均顯著低于其表達(dá)陰性的患者(P=0.002)。而EGFR基因擴(kuò)增和ALK基因重排與患者的整體生存率無(wú)關(guān)(P=0.309)(P=0.189)。4多因素分析結(jié)果顯示,MAGE-As表達(dá)、臨床分期和淋巴結(jié)轉(zhuǎn)移可做為NSCLC患者預(yù)后較差的獨(dú)立危險(xiǎn)因素。結(jié)論:MAGE-As蛋白可能是NSCLC的相關(guān)抗原,MAGE-As蛋白可作為非小細(xì)胞肺癌預(yù)后不良的判定指標(biāo)。第二部分肺癌患者外周血中MAGE-As基因的表達(dá)及其臨床意義目的:探討MAGE-As基因在肺癌患者外周血中的表達(dá)及其臨床意義。方法:1采用多重巢式RT-PCR(multi RT-nested PCR)方法檢測(cè)122例肺癌患者和30例健康人外周血中MAGE-As mRNA表達(dá)水平。2利用特異性酶切方法鑒定該家族成員MAGE-A1、-A2、-A3、-A4、和-A6的表達(dá)情況。結(jié)果:1 MAGE-As mRNA在肺癌患者外周血中表達(dá)率為17.21%(21/122),MAGE-As家族各成員在肺癌患者外周血中的表達(dá)順序?yàn)锳2A6A4A3A1。表達(dá)陽(yáng)性率分別為MAGE-A1 2.46%(3/122)、MAGE-A2 15.57%(19/122)、MAGE-A3 9.02%(11/122)、MAGE-A412.30%(15/122)、MAGE-A6 13.93%(17/122)。2肺癌患者外周血中MAGE-As mRNA的表達(dá)與臨床指標(biāo)間的相關(guān)性。肺癌患者外周血中MAGE-As mRNA的表達(dá)與患者臨床分期、腫瘤大小、淋巴結(jié)轉(zhuǎn)移、遠(yuǎn)端轉(zhuǎn)移、放化療以及年齡明顯相關(guān)(均P0.05)。外周血MAGE-As mRNA的表達(dá)率與肺癌患者的腫瘤類(lèi)型、吸煙、喝酒無(wú)明顯相關(guān)性(均P0.05)。3肺癌患者外周血中MAGE-A2、-A3、-A4和-A6 mRNA的表達(dá)與患者臨床分期、腫瘤大小、淋巴結(jié)轉(zhuǎn)移、遠(yuǎn)端轉(zhuǎn)移有明顯相關(guān)性(均P0.05)。另外,遠(yuǎn)端轉(zhuǎn)移組患者外周血中MAGE-A1的表達(dá)陽(yáng)性率顯著高于未轉(zhuǎn)移組(P0.05),放化療后肺癌患者外周血中MAGE-A2、-A3和-A6 mRNA的表達(dá)陽(yáng)性率均低于未接受放化療的患者(均P0.05)。結(jié)論:MAGE-As mRNA在肺癌患者外周血中的表達(dá)與肺癌預(yù)后相關(guān),有可能作為監(jiān)測(cè)肺癌預(yù)后的重要指標(biāo),以及檢測(cè)肺癌患者外周血循環(huán)腫瘤細(xì)胞的標(biāo)記。
[Abstract]:Cancer is a serious health safety problem for human beings. At present, cancer mortality is high, including lung cancer, colorectal cancer, prostate cancer, and breast cancer. These 4 cancers account for almost half of all cancer deaths. The new mortality rate of lung cancer is high in the global cancer deaths. With the development of medical science, immunization The treatment of Cancer/testis antigens (CTA) is the key to tumor immunotherapy. Cancer / testicular antigen (CTA) is restricted to the testis tissue in normal tissues and occasionally in normal tissues. The expression in the ovarian and placental tissues is not expressed in various tumor tissues, and has a specific expression pattern. Therefore, it has a potential advantage as a specific target for tumor immunotherapy. In recent years, we have been focusing on the expression of the melanoma antigen (MAGE) -A family in the melanoma phase of different tumor tissues. This study uses immunohistochemical staining and fluorescence in situ hybridization (fluorescent in situ hybridization, FISH) to detect non small cell lung cancer (non-small-cell lung cancer, NSCLC) and MAGE-As in the para cancerous tissues of non small cell lung cancer. The expression of 0 and A12, EGFR gene amplification and ALK gene rearrangement and the relationship with clinical biological indexes. The relationship between the expression of MAGE-As gene in peripheral blood of lung cancer patients and clinical prognosis is further explored. The main contents and results are as follows: the first part is the expression of MAGE-As in the tumor tissues of non small cell lung cancer patients and The clinical significance Objective: To investigate the expression of melanoma antigen (MAGE) -As in non-small cell lung cancer tumor tissue, and to analyze its relationship with the clinicopathological features and prognosis of the patients. Methods: 1 to buy the NSCLC tumor tissue of the Shanghai National Engineering Research Center and the corresponding biochip of the corresponding paracancerous tissue in 90 cases. Immunohistochemical staining was used to detect the expression of MAGE-As protein in NSCLC tumor tissues and corresponding para cancerous tissues..2 amplification and ALK gene rearrangement in NSCLC tumor tissues were detected by fluorescence in situ hybridization, and the relationship between MAGE-As expression and EGFR gene amplification and ALK rearrangement was analyzed. Results: 1 NSCLC tumor group. The expression of the positive expression of MAGE-As protein was 45.56% (41/90).2 MAGE-As protein and the clinicopathological features of the patients. There was no correlation between EGFR gene amplification and ALK gene rearrangement (P0.05).3 Log-Rank test. The survival period of NSCLC patients with positive MAGE-As protein expression was significantly lower than that of those with negative expression (P=0.002). Gene amplification and ALK gene rearrangement and the overall survival rate of patients (P=0.309) (P=0.189).4 multivariate analysis showed that MAGE-As expression, clinical stage and lymph node metastasis could be independent risk factors for poor prognosis in NSCLC patients. Conclusion: MAGE-As protein may be the associated antigen of NSCLC, and MAGE-As protein can be used as non small cell lung cancer. Evaluation index of poor prognosis. Expression of MAGE-As gene in peripheral blood of second lung cancer patients and its clinical significance: To explore the expression and clinical significance of MAGE-As gene in peripheral blood of patients with lung cancer. Methods: 1 using multiple nested RT-PCR (multi RT-nested PCR) Fang Fajian in 122 cases of lung cancer and 30 healthy people in peripheral blood MA GE-As mRNA expression level.2 was used to identify the expression of MAGE-A1, -A2, -A3, -A4, and -A6 in the family members by specific enzyme digestion. Results: the expression rate of 1 MAGE-As mRNA in peripheral blood of lung cancer patients was 17.21% (21/122). 2.46% (3/122), MAGE-A2 15.57% (19/122), MAGE-A3 9.02% (11/122), MAGE-A412.30% (15/122), MAGE-A6 13.93% (17/122).2, the correlation between the expression of MAGE-As mRNA in peripheral blood of the lung cancer patients and the clinical staging, tumor size, lymph node metastasis, distal metastasis, radiotherapy and chemotherapy in the peripheral blood of the patients with lung cancer The expression of MAGE-As mRNA in peripheral blood has no significant correlation with tumor type, smoking and drinking (P0.05) in patients with lung cancer (all P0.05) the expression of MAGE-A2, -A3, -A4 and -A6 mRNA in patients with.3 lung cancer has a significant correlation with the clinical stages, tumor size, lymph node metastasis and distal metastasis (P0.05). The positive rate of MAGE-A1 expression in peripheral blood of patients with distal metastasis was significantly higher than that in non metastasis group (P0.05). The positive rate of MAGE-A2, -A3 and -A6 mRNA in peripheral blood of lung cancer patients after radiotherapy and chemotherapy was lower than that of patients without chemotherapy (P0.05). Conclusion: the expression of MAGE-As mRNA in peripheral blood of lung cancer patients is related to the prognosis of lung cancer, and there is a possible correlation between the expression of MAGE-As mRNA in lung cancer patients and the prognosis of lung cancer. It can be used as an important indicator for monitoring the prognosis of lung cancer and a marker for detecting circulating tumor cells in peripheral blood of patients with lung cancer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R734.2

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