CCL18 in a Multiplex Urine-Based Assay for the Detection of Bladder Cancer

Abstract

The early detection of bladder cancer (BCa) is pivotal for successful patient treatment and management. Through genomic and proteomic studies, we have identified a number of bladder cancer-associated biomarkers that have potential clinical utility. In a case-control study, we examined voided urines from 127 subjects: 64 tumor-bearing subjects and 63 controls. The urine concentrations of the following proteins were assessed by enzyme-linked immunosorbent assay (ELISA); C-C motif chemokine 18 (CCL18), Plasminogen Activator Inhibitor 1 (PAI-1) and CD44. Data were compared to a commercial ELISA-based BCa detection assay (BTA-Trak©) and voided urinary cytology. We used analysis of the area under the curve of receiver operating characteristic curves to compare the ability of CCL18, PAI-1, CD44, and BTA to detect BCa in voided urine samples. Urinary concentrations of CCL18, PAI-1, and BTA were significantly elevated in subjects with BCa. CCL18 was the most accurate biomarker (AUC; 0.919; 95% confidence interval [CI], 0.8704-0.9674). Multivariate regression analysis highlighted CCL18 (OR; 18.31; 95% CI, 4.95-67.70, p<0.0001) and BTA (OR; 6.43; 95% CI, 1.86-22.21, p = 0.0033) as independent predictors of BCa in voided urine samples. The combination of CCL18, PAI-1 and CD44 improved the area under the curve to0.938. Preliminary results indicate that CCL18 was a highly accurate biomarker for BCa detection in this cohort. Monitoring CCL18 in voided urine samples has the potential to improve non-invasive tests for BCa diagnosis. Furthermore using the combination of CCL18, PAI-1 and CD44 may make the model more robust to errors to detect BCa over the individual biomarkers or BTA.

Correlation between serum level of chemokine (C-C motif) ligand 18 and poor prognosis in breast cancer

“…CCL-18 acts through autocrine and paracrine signaling, and participates in immunologic and inflammatory processes (Urquidi et al, 2012). Previous studies have shown that CCL-18 also has the ability affect tumorigenesis, and can affect the grade and prognosis of ovarian, colon, and gastric cancers.…”

MiR-1-3p inhibits the proliferation and invasion of bladder cancer cells by suppressing CCL2 expression

“…Targeted therapy acts on the genetic pathways responsible for BC, 4 which is regarded as the nextgeneration therapy for the disease with the help of genomic and proteomic techniques. 3,9 MicroRNA (miR) is a short non-coding RNA sequence which plays an important role in adjusting gene expressions. It binds to the 3′ untranslated region (UTR) of target messenger RNAs (mRNAs) and affects the corresponding transcription process.…”

A multiplex immunoassay for the non-invasive detection of bladder cancer.

“…Using commercial ELISA assay kits directed at the biomarker panel, we performed three independent experiments. First, we analyzed voided urines from 127 subjects (64 with BCa and 63 controls) and confirmed that 10 of the 14 biomarkers were significantly altered in BCa compared to controls [13][14][15][16]. Next, we reported the validation of the 10-biomarker diagnostic panel (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SDC1 and SERPINE1) in a large cohort of patients (n = 308; 102 BCa and 206 controls) including controls with diverse urologic conditions (e.g., urolithiasis, moderate-severe voiding symptoms, urinary tract infection and hematuria) [17].…”

“…We have reported the derivation and the validation of the urinary 10-biomarker BCa diagnostic signature in a number of studies with a total of over 800 subjects [13][14][15][16][17][18]. Recent work from our laboratory using quantitative immunohistochemical staining techniques for the detection of the signature proteins has shown a strong association of expression and malignancy in human bladder tumor tissues [27].…”