| Objective:Bladder cancer is one of the most common tumors of the urinary system in Chinese population. At the same time, its high morbidity and high recurrence rate brought a heavy economic burden to our social and patients. At present, cystoscopy is the gold standard diagnosis of bladder tumor. But it is not suitable for screening because of its potential complications. Although cytology has a high specificity, but the sensitivity is lower. Tumor markers, which in form of enzymes, hormones and antigens, were released in patients’ body environment during in the formation and development of carcinoma. It is significant to find more sensitive and specific, simple and noninvasive tumor markers for diagnosis of bladder cancer. Current studies believe that, Bladder cancer specific nuclear matrix proteins(BLCAs)specifically express in bladder tumor tissue, which BLCA-1 showed high sensitivity and specificity in diagnose of bladder cancer. This study aim to investigate the clinical application value of early diagnosis, treatment and monitoring for patients with muscle invasive bladder tumor(MIBC)through using enzyme-linked immunosorbent assay(ELISA)to analysis the BLCA-1 level in serum and urine and compared to BTA kit, which is a relatively mature method approved by FDA, and compared BLCA-4,which have been detected by Wang of our group. In order to laid theoretical foundation for further study of BLCA-1 to diagnose and treatment of bladder cancer.Methods:Among inpatients treated in our hospital’s Department of Urology from March 2014 to March 2015, 66 subjects were randomly selected. For the experimental group, there were 22 subjects with primary MIBC, including 16 men and 6 women with an average age of 64±11 years(range, 45-90 years). According to the 2004 World Health Organization grading method, 5 had low-grade, and 17 had high-grade tumors. According to the 2009 tumor node metastasis staging standard, 16 subjects were in stage T2 and 6 were in stage T3+T4. For control group A(normal control group), there were 22 healthy cases including 10 men and 12 women who had an average age of 41±14 years(range, 21-66 years). For control group B(BPH group), there were 22 patients with benign prostatic hyperplasia(BPH)who had an average age of 64±7 years(range, 52-81 years). Blood and urine samples were collected from all subjects above. Competitive enzyme-linked immunosorbent assay was used to determine BLCA-1 and BTA level in serum and urine of different groups. Detection of BLCA-4 expression in muscle invasive bladder cancer have been completed by Wang Xiaopeng of our laboratory. The experimental data of ours have comparability. Intergroup comparisons of measurement data were conducted using the rank-transformed nonparametric test. Intergroup comparisons of enumeration data, presented as odds ratios, were performed using Fisher exact test. All data were processed using SPSS version 19.0(SPSS, Inc.), and P values of <0.05 were considered statistically significant.Results:Median urinary BLCA-1 level in experimental group, control group A, and control group B were 1.479ng/ml,0.435ng/ml,0.709ng/ml, respectively; urinary BLCA-1 level was significantly higher in the experimental group compared with the other 2 groups(P<0.01), and was significantly higher in the control group B compared with the control group A(P<0.05). ROC curve shows that with a cut-off value of 0.946 ng/mL sensitivity and specificity of the urinary BLCA-1 for detection of bladder cancer were 77%(17/22)and 97%(41/44); Median serum BLCA-1 level in experimental group, control group A, and control group B were 6.621ng/ml,3.522ng/ml,5.611ng/ml, respectively; serum BLCA-1 level was significantly higher in the experimental group compared with the other 2 groups(P<0.05), and was significantly higher in the control group B compared with the control group A(P<0.05), and showing no significant difference between experimental group and control group B(P>0.05). ROC curve shows with a cutoff value of 4.537ng/m L sensitivity and specificity of the serum BLCA-1 for detection of bladder cancer were 86%(19/22)and 56%(26/44).Median urinary BTA level in experimental group, control group A, and control group B were 214.494ng/ml,9.384ng/ml,121.982ng/ml, respectively; urinary BTA level was significantly higher in the experimental group compared with the other 2 groups(P<0.05), and was significantly higher in the control group B compared with the control group A(P<0.05). ROC curve shows that with a cutoff value of 81.01ng/mL sensitivity and specificity of the urinary BTA for detection of bladder cancer were 77%(17/22)and 63%(28/44). Urinary BLCA-1 was irrelevant to sex, age, pathological grading and clinical stage(P>0.05). The level of serum BLCA-1 was higher in the high age(A≥60)and the high grade(P<0.05).The results of Fisher’s exact test showed that the specificity of urinary BLCA-1 was significantly higher than that of urinary BTA(P<0.05); and there is no significant difference based on sensitivity between both(P>0.05). Meanwhile, the sensitivity of the urinary BLCA-1 for detection of low-level MIBC was significantly higher than that in urinary BTA(P<0.05)(80%(4/5)vs 20%(1/5)), there was no significant difference based on specificity(88%(15/17)vs94%(16/17))(P>0.05).The diagnostic accuracy, positive predictive value, negative predictive value and Youden’s index of detect urinary BLCA-1 by ELISA were higher than that of urinary BTA. The results of Wang showed that detecting urinary BLCA-4 for diagnose bladder cancer with a sensitivity of 96%(22/24), and a specificity of 100%, but expression of BLCA-4 in serum showed no clinical value. And the sensitivity and specificity shows no difference between BLCA-1 and BLCA-4 in urinary by Fisher exact test(P>0.05).Conclusions:ROC curve shows that with a cut-off value of 0.946 ng/mL sensitivity and specificity of the urinary BLCA-1 for detection of bladder cancer were optimal. And urinary BLCA-1 was irrelevant to sex, age, pathological grading and clinical stageROC curve shows with a cutoff value of 4.537ng/mL sensitivity and specificity of the serum BLCA-1 for detection of bladder cancer were optimal. And the level of serum BLCA-1 was higher in the high age(A≥60) and the high gradeUrinary BLCA-1 showed high specificity compared with BTA(93% vs 64%).And the positive predictive value, negative predictive value, Youden index and accuracy of urinary BLCA-1 for detecting bladder cancer are higher than BTA.As a new tumor marker, BLCA-1 showed a high sensitivity and specificity for diagnosed of bladder cancer, and which has a high clinical value, and it is worth of further study. |
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