本文選題：LIMD2蛋白　切入點(diǎn)：非小細(xì)胞肺癌　出處：《第二軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：目的:探討LIMD2蛋白在手術(shù)切除的非小細(xì)胞肺癌中的表達(dá)及臨床意義。方法:收集福州總醫(yī)院2010年10月至2014年7月經(jīng)手術(shù)切除的NSCLC 141例,癌旁組織25例。使用HE染色對(duì)標(biāo)本中的腫瘤組織進(jìn)行檢測(cè),使用擴(kuò)增阻滯法(AMRS法)和實(shí)時(shí)熒光(PCR法)對(duì)腫瘤組織中的EGFR突變狀態(tài)進(jìn)行檢測(cè)。采用免疫組化法對(duì)組織中的LIMD2蛋白及E鈣黏素進(jìn)行檢測(cè)。Ki-67和VEGF在腫瘤組織中的表達(dá)以本院免疫組化報(bào)告為準(zhǔn)。LIMD2蛋白與臨床病理參數(shù)的關(guān)系采用卡方檢驗(yàn),DFS用Kaplan-Meier生存曲線述,LIMD2蛋白與E鈣粘素關(guān)系采用Spearman秩和檢驗(yàn),單因素和多因素COX回歸分析LIMD2蛋白、E鈣粘素和各病理參數(shù)與NSCLC術(shù)后DFS關(guān)系。采用雙側(cè)檢驗(yàn),P0.05認(rèn)為有統(tǒng)計(jì)學(xué)意義。結(jié)果:患者年齡分布27-80歲,中位發(fā)病年齡60歲。術(shù)后進(jìn)展105(74.5%)例,無進(jìn)展36(25.5%)例,術(shù)后DFS2.8-64.3個(gè)月,中位DFS15.9個(gè)月。腺癌84(59.6%)例,鱗癌57(40.4%)例,腫瘤細(xì)胞高中分化96例(68.1%),低分化45例(31.9%)。Ki-67高表達(dá)79例(56.0%),低表達(dá)62例(44.0%),Ki-67高表達(dá)在肺鱗癌(P=0.002)和低分化的腫瘤中更常見(P=0.000)。VEGF高表達(dá)74例(52.5%),低表達(dá)67例(47.5%),VEGF高表達(dá)在肺腺癌中更常見(P=0.042)。EGFR突變43例(30.5%),野生型98例(69.5%),EGFR突變?cè)谂?P=0.023)和腺癌中常見(P=0.000)。Ki-67、VEGF的表達(dá)水平和EGFR突變狀態(tài)與術(shù)后DFS無關(guān)。LIMD2在腫瘤組織中高表達(dá)71例(50.4%),低表達(dá)70例(49.6%),在癌旁組織中高表達(dá)7例(28.0%),低表達(dá)18例(72.0%),LIMD2在腫瘤組織中高表達(dá)較癌旁組織常見。E鈣黏素在腫瘤組織中高表達(dá)75例(53.2%),低表達(dá)66例(46.8%),在癌旁組織中高表達(dá)13例(52.0%),低表達(dá)12例(48.0%),E鈣黏素在兩種組織中表達(dá)無差異。腫瘤組織中LIMD2表達(dá)水平在不同N、TNM分期及腫瘤分化程度方面存在差異,LIMD2高表達(dá)常見于術(shù)后DFS短的患者中(P=0.033)。E鈣黏素表達(dá)水平在不同的T、N及TNM分期中表達(dá)水平存在差異,E鈣黏素高表達(dá)在術(shù)后較長(zhǎng)的DFS患者中常見(P=0.000)。在癌組織中LIMD2表達(dá)水平與E鈣黏素表達(dá)水平呈負(fù)相關(guān)(R=-0.42,P=0.000)。多因素回歸分析表明性別、T分期、TNM分期、腫瘤分化程度、LIMD2及E鈣黏素表達(dá)與NSCLC術(shù)后DFS相關(guān)。結(jié)論:在NSCLC中LIMD2可能抑制E鈣黏素表達(dá),LIMD2在腫瘤組織中表達(dá)越高術(shù)后DFS越短,LIMD2或許可以作為預(yù)測(cè)NSCLC術(shù)后復(fù)發(fā)的生物標(biāo)志物。
[Abstract]:Objective: to investigate the expression and clinical significance of LIMD2 protein in surgical resection of non-small cell lung cancer (NSCLC). Methods: 141 cases of NSCLC were surgically resected from October 2010 to July 2014 in Fuzhou General Hospital. He staining was used to detect tumor tissues in 25 cases of paracancerous tissues. The mutation status of EGFR in tumor tissues was detected by Amplification Block Assay (Amr) and Real time fluorescence PCR (RT PCR). Immunohistochemical method was used to detect LIMD2 protein and E-cadherin in tumor tissues. Ki-67 and VEGF were detected on the surface of tumor tissues. The relationship between LIMD2 protein and clinicopathological parameters was studied by chi-square test. The relationship between LIMD2 protein and E-cadherin was described by Kaplan-Meier survival curve. Spearman rank sum test was used to test the relationship between LIMD2 protein and E-cadherin. Univariate and multivariate COX regression analysis showed that LIMD2 protein E cadherin and pathological parameters were correlated with DFS after NSCLC. Bilateral test (P0.05) showed that there was statistical significance. Results: the age distribution of the patients was 27-80 years old, the median age of onset was 60 years old, and the postoperative progression was 105% 74.5% (P < 0.05). No progress was found in 36 cases, DFS2.8-64.3 month after operation, median DFS15.9 month, adenocarcinoma 849.6 cases, squamous cell carcinoma 5740.4). High expression of Ki-67 in 79 cases, high expression of Ki-67 in 62 cases, high expression of Ki-67 in 62 cases, high expression of P0. 0000. 002 in lung squamous cell carcinoma, high expression of P0.000.VEGF in 74 cases of poorly differentiated tumors, low expression of VEGF in 67 cases of lung adenocarcinoma, and low expression of VEGF in 67 cases of lung adenocarcinoma. The expression level of EGFR and EGFR mutation were not related to the postoperative DFS. LIMD2 was not related to the expression of DFS in tumor tissues. LIMD2 was highly expressed in tumor tissues in 71 cases, and low expression in 70 cases (49.6%), and was high in the adjacent tissues of carcinoma. The expression of EGFR mutation was not related to the expression of DFS in the tumor tissues after operation, while the expression of EGFR mutation in wild type 98 cases was 69.5%, and the expression level of EGFR mutation was high in the adjacent tissues of the carcinoma. The level of EGFR mutation was not related to the postoperative DFS. LIMD2 was highly expressed in the tumor tissues of 71 cases, and the low expression of 70 cases was 49.6% in the adjacent tissues. The high expression of LIMD2 in tumor tissues was higher than that in paracancerous tissues. There were 75 cases with high expression of E-cadherin in tumor tissues, 66 cases with low expression of calcitonin, 13 cases with high expression of LIMD2 in adjacent tissues, and 12 cases with low expression of E-cadherin in paracancerous tissues. There was no difference in the expression of LIMD2 between the two kinds of tissues. There were differences in the expression of LIMD2 in different tumor stages and tumor differentiation. The high expression of LIMD2 was more common in patients with short DFS after operation than in the patients with short DFS. There was significant difference in the expression of E-cadherin in TNM stage. The high expression of E-cadherin was common in patients with long postoperative DFS. There was a negative correlation between LIMD2 expression and E-cadherin expression in cancer tissues. Multivariate regression analysis showed that sex T staging was associated with TNM stage. The expression of LIMD2 and E-cadherin is related to the expression of E-cadherin after NSCLC. Conclusion: LIMD2 may inhibit E-cadherin expression in NSCLC. The higher the expression of LIMD2 in tumor tissues, the shorter DFS expression. LIMD2 may be a biomarker for predicting the recurrence of NSCLC.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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