本文選題：肝癌　切入點：miR-143　出處：《廣西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的原發(fā)性肝癌(Hepatocellular carcinoma)全球發(fā)病率逐年增長,在腫瘤相關(guān)死亡中位居第二位。如能對原發(fā)性肝癌進(jìn)行早期的診斷,就能使其治療方案得到很好的效果,這對于提高患者的生活質(zhì)量,并且延長其生存期都有很大幫助�，F(xiàn)今病理學(xué)檢查、影像學(xué)檢查和血清甲胎蛋白(alpha-feto protein,AFP)檢測等作為臨床上主要的診斷肝癌的方法,雖然AFP檢測特異性高,但有30%~40%的肝癌患者呈陰性。所以,各科研人員也認(rèn)識到不斷找尋更好更新的肝癌血清腫瘤標(biāo)記物非常有必要。到目前為止,國內(nèi)針對miR-143、miR-145在肝癌表達(dá)情況的研究較少。本研究探討了肝癌患者血清中的miR-143、miR-145表達(dá)水平,并闡明血清miR-143、miR-145與肝癌標(biāo)記物AFP、AST和ALT的關(guān)系,探討miR-143、miR-145與AFP聯(lián)合檢測在肝癌患者中的診斷價值,為HCC臨床診斷提供新的有效的分子標(biāo)志物。方法符合要求的肝癌、肝硬化患者各30例和30例同期健康對照的血清均被納入本研究,所有納入人群清晨空腹靜脈血離心得到上清液,按總RNA提取試劑盒說明書提取細(xì)胞總RNA,按逆轉(zhuǎn)錄試劑盒說明書將總RNA逆轉(zhuǎn)錄成c DNA,應(yīng)用實時熒光定量PCR方法檢測在肝癌、肝硬化患者和健康體檢者血清中的miR-143、miR-145的表達(dá)水平,所得實驗結(jié)果采用相對定量法進(jìn)行分析,miRNA表達(dá)量以2-△△Ct表示。使用受試者工作特征(ROC)曲線和曲線下面積(AUC)分析miR-143、miR-145表達(dá)水平和AFP聯(lián)合檢測對肝癌診斷的靈敏度和特異性,并確定最佳診斷閾值,miR-143、miR-145與AFP的一致性檢驗采用Kappa分析。結(jié)果miR-143和miR-145在肝癌患者血清表達(dá)水平最高,肝硬化次之,正常人最低,3組間比較差異有統(tǒng)計學(xué)意義(P0.05)。不同臨床分期肝癌患者其miR-143和miR-145表達(dá)水平無統(tǒng)計學(xué)差異(P0.05)。肝癌患者血清miR-143、miR-145表達(dá)水平與AFP、AST、ALT無顯著相關(guān)性(P0.05)?miR-143診斷肝癌的AUC為0.86,最佳閾值為1.30,敏感度為0.871,特異度為0.733。miR-145診斷肝癌的AUC為0.70,最佳閾值為1.05,敏感度為0.806,特異度為0.600。miR-143+AFP、miR-145+AFP、miR-143+miR-145+AFP對肝癌診斷效能均較高,其中miR-143+miR-145+AFP的診斷效能最高(AUC=0.994),但miR-143+AFP的診斷敏感度最高(敏感度=0.903)。結(jié)論1、miR-143和miR-145在肝癌患者血清表達(dá)水平最高。2、miR-143、miR-145診斷肝癌的敏感度與特異度均較高。提示:miR-143、miR-145與肝癌的發(fā)病密切相關(guān),并可作為肝癌有效的診斷標(biāo)記物,聯(lián)合檢測miR-143、miR-145及AFP可以更有效的檢測肝癌。
[Abstract]:Objective the global incidence of primary liver cancer (HCC) has been increasing year by year, and it ranks second in tumor-related deaths. It is of great help to improve the quality of life of patients and prolong their survival. Nowadays, pathological examination, imaging examination and serum alpha-feto protein protein (AFP) test are the main methods for the diagnosis of liver cancer. Although the specificity of AFP detection is high, 30% of HCC patients are negative. Therefore, researchers also realize that it is necessary to constantly search for better updated tumor markers in liver cancer serum. The expression of miR-143 miR-145 in serum of patients with liver cancer was studied, and the relationship between miR-143 miR-145 and liver cancer markers AFPNAST and ALT was elucidated. To explore the diagnostic value of miR-143 miR-145 combined with AFP in patients with liver cancer, and to provide a new and effective molecular marker for clinical diagnosis of HCC. Serum samples of 30 patients with liver cirrhosis and 30 healthy controls were included in this study. The supernatants were obtained by early morning fasting venous blood centrifugation in all subjects. Total RNA was extracted according to the instructions of the total RNA extraction kit, and the total RNA was reverse transcribed into c DNA according to the instructions of the reverse transcription kit. The expression of miR-143 miR-145 in serum of patients with liver cancer, liver cirrhosis and healthy persons was detected by real-time fluorescence quantitative PCR method. The results showed that the expression of miRNA was expressed as 2Ct by relative quantitative method. The expression level of miR-143 miR-145 and the sensitivity and specificity of combined detection of miR-143 miR-145 and AFP in the diagnosis of hepatocellular carcinoma were analyzed by using the roc curve and area under the curve. The best diagnostic threshold was determined. The consistency test between miR-143 miR-145 and AFP was analyzed by Kappa. Results the expression of miR-143 and miR-145 in serum of patients with liver cancer was the highest, followed by cirrhosis. There was no significant difference in the expression of miR-143 and miR-145 in patients with different clinical stages of liver cancer. There was no significant correlation between the expression of miR-143 miR-145 in serum and the level of alt in patients with liver cancer. The AUC of miR-143 was 0.86, the best threshold was 1.30, the sensitivity was 0.871, the specificity was 0.70 for 0.733.miR-145, the best threshold was 1.05, the sensitivity was 0.806, and the specificity was 0.600.miR-143 AFPmmiR-145 AFPmiR-143 miR-145 AFP for the diagnosis of HCC. The diagnostic efficacy of miR-143 miR-145 AFP was the highest, but the sensitivity of miR-143 AFP was the highest (sensitivity: 0.903). Conclusion\\\%\\%\%\% miR-143\%\%\%\% miR-@@. Is closely related to the onset of the disease, The combined detection of miR-143 miR-145 and AFP can be used as an effective diagnostic marker for HCC.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.7

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本文編號：1658368