聯(lián)合檢測尿液中腫瘤標(biāo)記物診斷膀胱癌的可行性研究
發(fā)布時間：2018-07-23 11:06
【摘要】：目的:全球范圍內(nèi),每年發(fā)生約38萬例膀胱惡性腫瘤,而在中國,膀胱癌是最多見的泌尿系腫瘤。膀胱癌的發(fā)病初期診斷和術(shù)后進行隨訪主要采用膀胱鏡檢查術(shù),但它價錢昂貴且是一個侵入性的手段;尿細胞學(xué)檢測方便,無創(chuàng),但靈敏度不是很高,這些缺陷限制了膀胱癌的早期診斷和治療。此外,膀胱癌的高復(fù)發(fā)率特點使得術(shù)后復(fù)發(fā)的監(jiān)測尤為重要,但目前仍缺乏相應(yīng)手段,這些問題使得一種新的檢測手段成為需求。人的體液以及組織中具有一些特異性的腫瘤標(biāo)記物(Tumormakers),它們可以用來特異性的檢測某種惡性疾病,正因為它們對某種惡性腫瘤具有特異性,故而臨床上常常應(yīng)用腫瘤標(biāo)記物來診斷特定腫瘤,并可以為腫瘤的治療及預(yù)后進行評估,是以腫瘤標(biāo)志物逐漸得到廣泛的關(guān)注,成為當(dāng)前熱門的研究方向。本研究主要通過ELISA的方法檢測尿液中NMP22、CD44、CK20、CEACAM1和BTA五種腫瘤標(biāo)記物在膀胱癌患者尿液中的表達情況,并探討上述五種標(biāo)記物不同組合在膀胱癌診斷中的臨床意義,為后續(xù)開發(fā)更為有效的能同時檢測多種腫瘤標(biāo)記物的試劑盒提供理論依據(jù)。方法:選取了2015年12月至2016年6月期間因懷疑膀胱腫瘤收治于天津醫(yī)科大學(xué)第二醫(yī)院的患者,經(jīng)膀胱鏡活檢或TURBT術(shù)后病理診斷為膀胱癌的64名患者納入本研究,設(shè)為腫瘤組;并選取20名非泌尿系腫瘤的患者作為對照組。應(yīng)用酶聯(lián)免疫吸附測定法(enzyme linked immunosorbent assay)分別檢測兩組患者尿液樣本中NMP22、CD44、CK20、CEACAM1和BTA的表達水平,通過吖啶橙法(AO-F)行尿脫落細胞檢查。應(yīng)用SPSS19.0軟件繪制受試者工作曲線(ROC),使用約登指數(shù)(Youden index)來計算5種腫瘤標(biāo)記物的臨界值(Cutoff),從而比較這五種腫瘤標(biāo)記物以及不同組合聯(lián)合診斷膀胱癌的準(zhǔn)確性。應(yīng)用秩和檢驗或費氏確切概率法分析五種腫瘤標(biāo)記物與患者臨床病理特征之間的關(guān)系。結(jié)果:1、NMP22、CD44、CK20、CEACAM1和BTA五種腫瘤標(biāo)記物在腫瘤組的濃度顯著高于對照組,差異具有統(tǒng)計學(xué)意義(P0.05)。2、NMP22、BTA、CK20、CD44、CEACAM1的曲線下面積(AUC)分別為0.752、0.820、0.773、0.859、0.724,由此可見這幾種種標(biāo)記物比較,NMP22檢測膀胱癌的陽性率最高,達到84.3%,但特異度卻很低,僅為55%。而尿脫落細胞AO-F法檢測膀胱癌的特異度最高為100%,但它檢測膀胱癌的陽性率卻是6種腫瘤標(biāo)記物中最低的,僅為60.9%。依據(jù)AUC比較,CD44的檢測價值最大,當(dāng)CD44取cutoff值為348.8pg/ml時,其敏感度可達82.8%,特異度為85%。3、尿脫落細胞AO-F法對于低分級尿路上皮癌的檢測敏感度很低,僅為40%,而在高級別膀胱癌中的診斷敏感度為70.5%,兩者有統(tǒng)計學(xué)差異(p=0.028)。尿AO-F法和CEACAM1檢測膀胱癌的敏感度隨腫瘤分期升高而逐漸增加,但其他各項指標(biāo)卻沒有發(fā)現(xiàn)這種趨勢。4、BTA、CD44、CK20三項聯(lián)合檢測時,敏感度為96.8%,特異度為80.0%。結(jié)論:1、應(yīng)用ELISA法檢測尿液中NMP22、BTA、CK20、CD44、CEACAM1這5種腫瘤標(biāo)志物對膀胱癌的診斷具有一定的臨床意義。2、應(yīng)用1種標(biāo)記物檢測膀胱癌,CD44較其它4種標(biāo)記物的價值最大3、CEACAM1對高分期膀胱癌的敏感度更高,尿脫落細胞AO-F檢測對高分期、高分級膀胱癌的檢測敏感度更高。4、CD44、CK20、BTA三者聯(lián)合對膀胱癌的檢測具有較高的臨床意義。
[Abstract]:Objective: around 380 thousand cases of malignant bladder cancer occur annually worldwide, and bladder cancer is the most common urological tumor in China. Cystoscopy is mainly used in the early diagnosis and postoperative follow-up of bladder cancer, but it is expensive and an invasive hand; urine cytology is convenient and noninvasive, but the sensitivity is not It is very high, these limitations limit the early diagnosis and treatment of bladder cancer. In addition, the high recurrence rate of bladder cancer is particularly important for the monitoring of postoperative recurrence, but there is still a lack of corresponding means. These problems make a new detection method a demand. Human body fluid and group have some specific tumor markers (Tumorma KERS), they can be used to detect certain malignant diseases specifically. Because they are specific to a certain malignant tumor, they often use tumor markers to diagnose specific tumors, and can evaluate the treatment and prognosis of the tumor. It is gradually gaining extensive attention and becoming a hot research topic. The purpose of this study is to detect the expression of five tumor markers in urine of bladder cancer patients in urine by using ELISA method, and to explore the clinical significance of the different combinations of these five markers in the diagnosis of bladder cancer and to detect a variety of tumor markers at the same time for the subsequent development of the five kinds of markers. Methods: 64 patients who were admitted to Second Hospital Affiliated to Tianjin Medical University from December 2015 to June 2016 were enrolled in this study for bladder cancer with cystoscopy or TURBT, and 20 patients with non urinary tumors were selected as tumor groups. In the control group, the expression of NMP22, CD44, CK20, CEACAM1 and BTA in urine samples of two groups of two patients was detected by enzyme linked immunosorbent assay (linked immunosorbent assay), and the urine exfoliative cells were examined by acridine orange (AO-F). The working curve (ROC) was plotted with SPSS19.0 software, and the yonen index was used. The critical value of 5 tumor markers (Cutoff) was calculated to compare the accuracy of the five tumor markers and the combination of different combinations in the diagnosis of bladder cancer. The relationship between the five tumor markers and the clinicopathological features of the five tumor markers was analyzed by the rank sum test or the Fisher exact probability method. Results: 1, NMP22, CD44, CK20, CEACAM1, and BTA five tumor markers The concentration of the records in the tumor group was significantly higher than that in the control group. The difference was statistically significant (P0.05).2, NMP22, BTA, CK20, CD44, and CEACAM1 under the curves of AUC, respectively, 0.752,0.820,0.773,0.859,0.724. Thus, the positive rate of bladder cancer detected by NMP22 was the highest, reaching 84.3%, but the specificity was very low, only 55%.. The highest specificity of urinary exfoliative cell AO-F method for detecting bladder cancer was 100%, but the positive rate of bladder cancer detection was the lowest in 6 tumor markers. Only 60.9%. was compared with AUC, and CD44 was of the greatest value. When CD44 was 348.8pg/ml, its sensitivity was 82.8%, specificity was 85%.3, and urine exfoliative cells AO-F method. The detection sensitivity of low grade urothelial carcinoma was very low, only 40%, and the diagnostic sensitivity in advanced bladder cancer was 70.5%. There was a statistical difference between them (p=0.028). The sensitivity of urinary AO-F and CEACAM1 to bladder cancer increased with the increase of tumor stage, but the other indicators did not find the trend.4, BTA, CD44, CK20 three. The sensitivity of the joint examination was 96.8% and the specificity was 80.0%. conclusion: 1. The use of ELISA to detect NMP22 in urine, BTA, CK20, CD44, CEACAM1 has certain clinical significance for the diagnosis of bladder cancer, and the use of 1 markers for the detection of bladder cancer, the maximum value of CD44 compared with the other 4 markers is 3, CEACAM1 for high staging bladder cancer. The sensitivity of AO-F in urine exfoliative cells is higher than that of high staging, high grade bladder cancer, and.4, CD44, CK20, BTA three are of high clinical significance for the detection of bladder cancer.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.14
本文編號：2139204
[Abstract]:Objective: around 380 thousand cases of malignant bladder cancer occur annually worldwide, and bladder cancer is the most common urological tumor in China. Cystoscopy is mainly used in the early diagnosis and postoperative follow-up of bladder cancer, but it is expensive and an invasive hand; urine cytology is convenient and noninvasive, but the sensitivity is not It is very high, these limitations limit the early diagnosis and treatment of bladder cancer. In addition, the high recurrence rate of bladder cancer is particularly important for the monitoring of postoperative recurrence, but there is still a lack of corresponding means. These problems make a new detection method a demand. Human body fluid and group have some specific tumor markers (Tumorma KERS), they can be used to detect certain malignant diseases specifically. Because they are specific to a certain malignant tumor, they often use tumor markers to diagnose specific tumors, and can evaluate the treatment and prognosis of the tumor. It is gradually gaining extensive attention and becoming a hot research topic. The purpose of this study is to detect the expression of five tumor markers in urine of bladder cancer patients in urine by using ELISA method, and to explore the clinical significance of the different combinations of these five markers in the diagnosis of bladder cancer and to detect a variety of tumor markers at the same time for the subsequent development of the five kinds of markers. Methods: 64 patients who were admitted to Second Hospital Affiliated to Tianjin Medical University from December 2015 to June 2016 were enrolled in this study for bladder cancer with cystoscopy or TURBT, and 20 patients with non urinary tumors were selected as tumor groups. In the control group, the expression of NMP22, CD44, CK20, CEACAM1 and BTA in urine samples of two groups of two patients was detected by enzyme linked immunosorbent assay (linked immunosorbent assay), and the urine exfoliative cells were examined by acridine orange (AO-F). The working curve (ROC) was plotted with SPSS19.0 software, and the yonen index was used. The critical value of 5 tumor markers (Cutoff) was calculated to compare the accuracy of the five tumor markers and the combination of different combinations in the diagnosis of bladder cancer. The relationship between the five tumor markers and the clinicopathological features of the five tumor markers was analyzed by the rank sum test or the Fisher exact probability method. Results: 1, NMP22, CD44, CK20, CEACAM1, and BTA five tumor markers The concentration of the records in the tumor group was significantly higher than that in the control group. The difference was statistically significant (P0.05).2, NMP22, BTA, CK20, CD44, and CEACAM1 under the curves of AUC, respectively, 0.752,0.820,0.773,0.859,0.724. Thus, the positive rate of bladder cancer detected by NMP22 was the highest, reaching 84.3%, but the specificity was very low, only 55%.. The highest specificity of urinary exfoliative cell AO-F method for detecting bladder cancer was 100%, but the positive rate of bladder cancer detection was the lowest in 6 tumor markers. Only 60.9%. was compared with AUC, and CD44 was of the greatest value. When CD44 was 348.8pg/ml, its sensitivity was 82.8%, specificity was 85%.3, and urine exfoliative cells AO-F method. The detection sensitivity of low grade urothelial carcinoma was very low, only 40%, and the diagnostic sensitivity in advanced bladder cancer was 70.5%. There was a statistical difference between them (p=0.028). The sensitivity of urinary AO-F and CEACAM1 to bladder cancer increased with the increase of tumor stage, but the other indicators did not find the trend.4, BTA, CD44, CK20 three. The sensitivity of the joint examination was 96.8% and the specificity was 80.0%. conclusion: 1. The use of ELISA to detect NMP22 in urine, BTA, CK20, CD44, CEACAM1 has certain clinical significance for the diagnosis of bladder cancer, and the use of 1 markers for the detection of bladder cancer, the maximum value of CD44 compared with the other 4 markers is 3, CEACAM1 for high staging bladder cancer. The sensitivity of AO-F in urine exfoliative cells is higher than that of high staging, high grade bladder cancer, and.4, CD44, CK20, BTA three are of high clinical significance for the detection of bladder cancer.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.14
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