The Expression And Clinical Significance Of BLCA-1 In Urine And Serum For Non Muscle-Invasive Bladder Cancer

Objective:To probe the characteristic and clinical value for non muscle-invasive bladder cancer,calculating the cutoff value, sensitivity and specificity of BLCA-1, we aim to provide data to clinical application for BLCA-1.Methods:22 patients with non muscle-invasive bladder cancer were enrolled as cancer group, a total of 44 donors including 22 patients with benign prostate hyperplasia(BPH) and 22 healthy donors enrolled as control group, which were reassigned to control group A(22 BPH patients) and control group B(22 healthy donors), which were in hospital from March 2014 to March 2015. Urine and serum samples of all groups were collected at 6 a.m. day 1 after enrolled. Supernatant liquid was extracted after precipitation by centrifugation at 3000RPM/sec. Using competitive enzyme-linked immunosorbent assay(ELISA) BLCA-1 was detected from urine and serum samples and compared between groups. And compare of BLCA-1 was conducted between non muscle-invasive bladder cancer and muscle-invasive bladder cancer patients and between BLCA-1 and BLCA-4 for non muscle-invasive bladder cancer patients(this phase trial has been accomplished in our lab using the same method and samples). Using double antibody sandwich enzyme-linked immunosorbent assay(ELISA) bladder cancer antigen(BTA) was detected from urine samples in all groups. After receiver operating characteristic(ROC) curve was produced, calculated were cutoff value, sensitivity, specificity and area under the curve(AUC) of urine BLCA-1, serum BLCA-1 and urine BTA.Results:Urine samples: BLCA-1 was associated higher expression with cancer group than with control group(Median density 1.64ng/ml vs 0.54ng/ml, P<0.05), higher with control group A than with control group B(Median density 0.71ng/ml vs 0.44ng/ml, P<0.05) and BPH patients were associated with lower expression of BLCA-1 than non muscle-invasive bladder cancer patients(P<0.05). Serum samples: BLCA-1 was associated higher expression with cancer group than with control group(Median density 5.48ng/ml vs 4.16ng/ml, P<0.05), higher with control group A than with control group B(Median density 5.61ng/ml vs 3.52ng/ml,P<0.05). But BLCA-1 expressions with cancer group and control group were similar(P>0.05). The median density value of BLCA-1 from urine of muscle-invasive bladder cancer patients was 1.48ng/ml, serum 6.62ng/ml, which were not significantly higher than non muscle-invasive bladder cancer(P>0.05). The median density value of BLCA-4 from urine of non muscle-invasive bladder cancer patients was 0.76ng/ml, serum 5.68ng/ml, which were not significantly higher than BLCA-1 for non muscle-invasive bladder cancer patients. BLCA-1 of non muscle-invasive bladder cancer did not appear to correlate with cancer grade or stage(P>0.05). Comparisons of sensitivity and specificity between urine BLCA-1, serum BLCA-1 and urine BTA: ROC curve of urine BCLA-1: using a cutoff density value of 1.0ng/ml, BLCA-1 was detected from 13 of 22 non muscle-invasive bladder cancer patients and 3 of 44 BPH or healthy donors, resulting in a teat of 59% sensitivity, 93 specificity and 0.757 AUC. ROC curve of serum BCLA-1: using a cutoff density value of 4.5ng/ml, BLCA-1 was detected from 19 of 22 non muscle-invasive bladder cancer patients and 19 of 43 BPH or healthy donors(1 sample was removed as hemolysis happened in the blood sample), resulting in a teat of 86% sensitivity, 56 specificity and 0.735 AUC. ROC curve of urine BTA: using a cutoff density value of 90.3ng/ml, BTA was detected from 12 of 22 non muscle-invasive bladder cancer patients and 14 of 42 BPH or healthy donors(a lot of white floccule arose in 2 urine samples after melting which were removed), resulting in a teat of 55% sensitivity, 67 specificity and 0.614 AUC. Comparisons between both serum BLCA-1 and urine BLCA-1 to urine BTA: serum BLCA-1 resulted in a higher sensitivity than urine BTA(P<0.05), and a similar specificity with urine BTA(P>0.05). Urine BLCA-1 resulted in a similar sensitivity with urine BTA(P>0.05) and higher specificity than urine BTA(P<0.05).Conclusions:1. BLCA-1 as a novel bladder tumor marker based serum and urine, indicating certain values for non muscle-invasive bladder cancer diagnose.2. AT cutoff density value of 1.0ng/ml, urine BLCA-1 resulted with high specificity and similar sensitivity compared with BTA. And at cutoff density value of 4.5ng/ml, serum BLCA-1 resulted with high sensitivity and similar specificity compared with BTA.3. BLCA-1 did not indicate values of correlation to cancer grade or stage.4. BLCA-1 densities of non muscle-invasive bladder cancer in nether urine or serum were not significantly different from muscle-invasive bladder cancer.5. Difference between BLCA-1 and BLCA-4 was not significant of non muscle-invasive bladder cancer.