本文選題：腎細胞癌 + 血清��； 參考：《新疆醫(yī)科大學》2017年博士論文

【摘要】：目的:通過回顧性分析我中心近10年收治的1005例腎細胞癌患者臨床資料,了解新疆地區(qū)腎細胞癌患者臨床特點、病理類型、種族特征等流行病學特點。檢測腎細胞癌患者血清中miR-106a與miR-21的表達水平,分析其與健康人群中的表達差異,評價其能否用于腎細胞癌的早期診斷;同時檢測miR-106a、mi R-21在手術前、后的表達水平變化,并研究其與臨床病理特征間的相互關系及臨床應用價值。方法:回顧性分析2006年1月至2015年12月就診于我院且行手術治療的1005例新發(fā)腎細胞癌患者的臨床和病理學特點,分別對性別構成、發(fā)病年齡、城鄉(xiāng)分布、民族構成、危險因素、治療方式、病理特征進行分析。并以2013年2月至2015年2月期間在我中心收集的30例新診斷為腎細胞癌患者的術前血清樣本作為實驗組,另外收集30例健康體檢者的血清樣本作為對照組,采用實時熒光定量PCR技術檢測各組血清樣本中miR-106a、miR-21表達水平,分析其在腎細胞癌及健康人群中的表達是否存在差異。對上述30例實驗組患者再對應的收集其術后1個月、6個月血清樣本作為本研究的術后組,分別檢測各血清樣本中術后1個月、6個月miR-106a、mi R-21表達水平,分析其表達水平與術前組間的差異以及與病理特征的相關性。結果:1055例腎細胞癌患者中男性患者占672例(66.9%),女性患者333例(33.1%),男女比例為2.02:1.00;發(fā)病年齡12歲~88歲,平均年齡54.2歲,高發(fā)年齡為40歲~60歲;城市地區(qū)患者人數(shù)為806例,農村地區(qū)患者人數(shù)為199例,城市地區(qū)發(fā)病率為農村地區(qū)的4.1倍;2006年就診41例(4.1%),2007年就診55例(5.5%),2008年就診81例(8.1%),2009年就診107例(10.6%),2010年就診115例(11.4%),2011年就診125例(12.4%),2012年就診94例(9.4%),2013年就診111例(11.0%),2014年就診137例(13.6%),2015年就診139例(13.8%),按患者就診年份排序,可見就診人數(shù)逐年升高;民族構成中漢族605例(60.1%),少數(shù)民族400例(39.8%),漢族構成比例較少數(shù)民族高。不同人口特征腎細胞癌患者的病理類型進行比較,結果顯示隨著年齡的增長,腎細胞癌患者中透明細胞癌的比例呈上升趨勢(p0.05);漢族患者中透明細胞癌所占比例顯著高于少數(shù)民族患者(p0.05);男性和女性腎細胞癌患者病理類型的差異無統(tǒng)計學意義(p0.05)。城市和鄉(xiāng)鎮(zhèn)腎細胞癌患者病理類型的差異無統(tǒng)計學意義(p0.05)。城市和鄉(xiāng)鎮(zhèn)腎細胞癌患者的臨床分期和病理分級進行比較,結果顯示相對于城市患者,鄉(xiāng)鎮(zhèn)患者的臨床分期較晚,病理分級較高,其差異有統(tǒng)計學意義(p0.05)。腎細胞癌患者根據(jù)是否吸煙、是否有高血壓和是否有糖尿病等情況分組,比較不同組患者的臨床分期和病理分級,結果顯示其差異無統(tǒng)計學意義(p0.05),即吸煙、高血壓和糖尿病等特征對腎細胞癌患者的臨床分期和病理分級無影響。手術方式隨年變化趨勢可見開放手術比例逐年下降,而腔鏡手術比例逐年上升;手術種類隨年變化趨勢可見根治術比例逐年下降,而保留腎單位手術比例逐年上升;患者住院天數(shù)也在隨年逐漸下降。腎細胞癌與健康對照組外周血mir-106a、mir-21測定結果顯示,腎細胞癌組血清中mir-106a的相對表達量為8.87(2.71~12.68),健康對照組外周血清mir-106a的相對表達量為0.87(0.31~2.13),與對照組相比較,腎細胞癌組血清mir-106a的相對表達量呈明顯高表達,兩組相對表達量差異具有統(tǒng)計學意義(z=-4.728,p=0.0001);在腎細胞癌組中,mirna-106a表達下調者有4例(13.3%),而表達量上調有26例(86.7%)。腎細胞癌組血清中mir-21的相對表達量為8.49(3.92~16.68),健康對照組中血清mirna-21的相對表達量為0.79(0.69~3.60),腎細胞癌組中mir-21相對表達量與對照組相比,其表達水平明顯增高,其相對表達量差異具有統(tǒng)計學意義(z=-4.727,p=0.0001);根據(jù)mir-106a的表達量差異來繪制roc曲線,結果顯示其曲線下面積(auc)為0.801(95%ci:0.710~0.963,p=0.0001),靈敏度為0.750,特異度為0.814,約登指數(shù)為0.564。根據(jù)mir-21的表達量差異來繪制roc曲線,結果顯示其曲線下面積(auc)為0.854(95%ci:0.786~0.947,p=0.0001),靈敏度為0.795,特異度為0.907,約登指數(shù)為0.702,采用mir-106a與mir-106a進行聯(lián)合檢測,其結果顯示系列實驗中靈敏度下降為0.596,特異度為上升為0.983,約登指數(shù)為0.579;平行實驗中靈敏度提高為0.949,特異度下降為0.738,約登指數(shù)為0.687。進一步檢測腎細胞癌患者對應術后1個月、6個月的外周血mir-106a、mir-21表達水平,術后1月組中mir-106a相對表達量為1.12(0.38~2.57),mir-21相對表達量為0.61(0.42~1.07),與健康對照組比較,術后1月組中mir-106a(z=-0.214,p=0.708)及mir-21(z=-1.301,p=0.272)表達水平差異沒有統(tǒng)計學意義;與術前組相比,術后1月組mir-106a(z=-4.218,p=0.0001)及mir-21(z=-3.119,p=0.002)表達水平明顯下降,其差異具有統(tǒng)計學意義;術后6個月組中mir-106a相對表達量為1.01(0.23~2.44),mir-21相對表達量為0.71(0.39~1.27),與健康對照組比較,術后6月組中miR-106a(Z=-0.232,P=0.874)及miR-21(Z=-1.221,P=0.291)表達水平差異無統(tǒng)計學意義。miR-106a、mi R-21在腎細胞癌患者外周血清的表達與腫瘤的組織病理學分級、臨床分期無關(P0.05)。結論:腎細胞癌患者血清中miR-106a和miR-21的表達水平明顯上調,ROC曲線分析提示其已經(jīng)達到臨床應用價值,是腎細胞癌可選的分子標志物。血清miR-106a和mi R-21的表達水平在切除腫瘤病灶后均明顯下降,并在術后表達水平穩(wěn)定,提示其有望用于術后隨訪監(jiān)測。
[Abstract]:Objective: through a retrospective analysis of the clinical data of 1005 cases of renal cell carcinoma in our center in recent 10 years, the clinical characteristics, pathological types and racial characteristics of renal cell carcinoma in Xinjiang were analyzed, and the expression of miR-106a and miR-21 in the serum of renal cell carcinoma patients was detected and the difference of expression in the healthy population was analyzed. To evaluate whether it can be used in the early diagnosis of renal cell carcinoma, and to detect the changes in the expression level of miR-106a, MI R-21 before and after operation, and to study the relationship between the clinicopathological features and the clinical application value. Methods: a retrospective analysis of 1005 cases of new renal cell carcinoma in our hospital from January 2006 to December 2015 and the operation treatment of renal cell carcinoma was reviewed. The clinical and pathological features of the patients were analyzed in terms of gender composition, age of onset, urban and rural distribution, ethnic composition, risk factors, treatment and pathological features, and 30 newly diagnosed patients with renal cell carcinoma were collected in our center from February 2013 to February 2015 as experimental group, and 30 cases of health were collected. The serum samples of the examiners were used as the control group. The expression of miR-106a and miR-21 in the serum samples of each group was detected by real time fluorescence quantitative PCR. The difference in the expression of the serum samples in the renal cell carcinoma and the healthy population was analyzed. The serum samples of the 30 patients in the experimental group were collected for 1 months after the operation, and the serum samples were taken as this study for 6 months. After operation, the expression level of miR-106a and MI R-21 was detected in 1 months, 6 months after operation, and the correlation between the expression level and the preoperative group and the pathological features were analyzed. Results: 1055 cases of renal cell carcinoma were male 672 cases (66.9%), women 333 cases (33.1%), male and female ratio 2.02:1.00; age 12. ~88 years old, the average age of 54.2 years and the age of 40 years old at the age of 40 years, 806 cases in urban areas, 199 in rural areas, 4.1 times in the urban area, 41 in 2006 (4.1%), 55 in 2007 (5.5%), 81 in 2008 (8.1%), 2009 for 107 cases (10.6%) and 2010 visits in 2010. In 2011, there were 125 cases (12.4%), 94 cases (9.4%) in 2012, 111 cases in 2013 (11%), 137 in 2014 (13.6%), 139 in 2015 (13.8%). According to the year of the patients, the number of patients was increased year by year, 605 (60.1%) in the ethnic group and minority 400 cases (39.8%), and the proportion of Han nationality was higher than that of minority nationalities. The pathological types of the patients with human renal cell carcinoma were compared. The results showed that the proportion of clear cell carcinoma in the patients with renal cell carcinoma increased with age (P0.05), and the proportion of clear cell carcinoma in Han patients was significantly higher than that of ethnic minority patients (P0.05), and the pathological types of renal cell carcinoma in male and female were different. Statistical significance (P0.05). The pathological types of renal cell carcinoma patients in cities and towns were not statistically significant (P0.05). The clinical stages and pathological grades of renal cell carcinoma patients in cities and towns were compared. The results showed that compared with urban patients, the clinical stages of township patients were late, and the pathological grades were higher, and the difference was statistically significant (P0.05 Patients with renal cell carcinoma were divided into groups according to whether they were smoking, whether there were hypertension or whether there was diabetes. The clinical stages and pathological grades of different groups were compared. The results showed that the difference was not statistically significant (P0.05), that is, smoking, hypertension and diabetes had no effect on the clinical staging and pathological classification of patients with renal cell carcinoma. The rate of open operation decreased year by year, and the proportion of endoscopic surgery increased year by year, and the trend of radical operation decreased year by year, while the proportion of kidney preserving operation increased year by year, and the number of hospitalization days decreased gradually. The peripheral blood of renal cell carcinoma and healthy control group was mir-106a, Mir The relative expression of mir-106a in the serum of renal cell carcinoma group was 8.87 (2.71~12.68), and the relative expression of serum mir-106a in the healthy control group was 0.87 (0.31~2.13). Compared with the control group, the relative expression of serum mir-106a in the renal cell carcinoma group was significantly higher than that of the control group. The difference of the relative expression of the two groups was statistically significant, and the difference of the relative expression of the two groups was statistically significant. Z=-4.728 (p=0.0001); in the renal cell carcinoma group, the expression of mirna-106a expression was 4 (13.3%), and the expression was up to 26 (86.7%). The relative expression of miR-21 in the serum of the renal cell carcinoma group was 8.49 (3.92~16.68), the relative expression of miRNA-21 in the healthy control group was 0.79 (0.69~3.60), and the relative expression of miR-21 in the renal cell carcinoma group and the relative expression of miR-21 in the renal cell carcinoma group. The expression level of the control group was significantly higher than that in the control group (z=-4.727, p=0.0001), and the ROC curve was drawn according to the difference of mir-106a expression. The results showed that the area under the curve (AUC) was 0.801 (95%ci:0.710~0.963, p=0.0001), the sensitivity was 0.750, the specificity was 0.814, and the Jordan index was 0.564. based mir-. 21 of the difference in expression to draw the ROC curve, the results show that the area under the curve (AUC) is 0.854 (95%ci:0.786~0.947, p=0.0001), the sensitivity is 0.795, the specificity is 0.907, and the Jordan index is 0.702. The combined detection of mir-106a and mir-106a shows that the sensitivity of the series is 0.596, the specificity rises to 0.983, about 0.983. The index was 0.579, the sensitivity of the parallel experiment was 0.949, the specificity decreased to 0.738, and the mir-106a index was 0.687., and the expression level of mir-106a and miR-21 in the peripheral blood was 1.12 (0.38~2.57) in the January group, and the relative expression of miR-21 was 0.61 (0.42~1.07) in the January group. Compared with the healthy control group, there was no significant difference in the expression level of mir-106a (z=-0.214, p=0.708) and miR-21 (z=-1.301, p=0.272) in the January group. Compared with the pre operation group, the level of mir-106a (z=-4.218, p=0.0001) and miR-21 (z=-3.119, p=0.002) in the January group decreased significantly, and the difference was statistically significant; 6 months after the operation, the difference was statistically significant. The relative expression of 106A was 1.01 (0.23~2.44), and the relative expression of miR-21 was 0.71 (0.39~1.27). Compared with the healthy control group, there was no significant difference in the expression level of miR-106a (Z=-0.232, P=0.874) and miR-21 (Z=-1.221, P=0.291) in the June group, and the expression of the peripheral blood serum and the histopathology of the tumor in the patients with renal cell carcinoma. P0.05. Conclusion: the expression level of miR-106a and miR-21 in the serum of renal cell carcinoma patients is obviously up-regulated. The ROC curve analysis suggests that it has reached clinical application value. It is an optional molecular marker of renal cell carcinoma. The expression level of serum miR-106a and MI R-21 decreased significantly after the tumor resection, and in the postoperative table. The level is stable, suggesting that it is expected to be used for postoperative follow-up monitoring.
【學位授予單位】：新疆醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R737.11

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