Claudia Andl
Faculty Member
Last active: 10/13/2015

Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer.

Arnold SA, Loomans HA, Ketova T, Andl CD, Clark PE, Zijlstra A
Clin Exp Metastasis. 2016 33 (1): 29-44

PMID: 26456754 · PMCID: PMC4742427 · DOI:10.1007/s10585-015-9754-x

The extracellular matrix protein fibronectin (FN) contributes to the structural integrity of tissues as well as the adhesive and migratory functions of cells. While FN is abundantly expressed in adult tissues, the expression of several alternatively spliced FN isoforms is restricted to embryonic development, tissue remodeling and cancer. These FN isoforms, designated ED-A and ED-B, are frequently expressed by cancer cells, tumor-associated fibroblasts and newly forming blood vessels. Using a highly sensitive collagen-based indirect ELISA, we evaluated the correlation of urinary ED-A and ED-B at time of cystectomy with overall survival in patients with high-grade bladder cancer (BCa). Detectable levels of total FN as well as ED-A and ED-B were found in urine from 85, 73 and 51 % of BCa patients, respectively. The presence of urinary ED-A was a significant independent predictor of 2-year overall survival (OS) after adjusting for age, tumor stage, lymph node stage, and urinary creatinine by multivariable Logistic Regression (p = 0.029, OR = 4.26, 95 % CI 1.16-15.71) and improved accuracy by 3.6 %. Furthermore, detection of ED-A in the urine was a significant discriminator of survival specifically in BCa patients with negative lymph node status (Log-Rank, p = 0.006; HR = 5.78, 95 % CI 1.39-24.13). Lastly, multivariable Cox proportional hazards analysis revealed that urinary ED-A was an independent prognostic indicator of 5-year OS rate for patients with BCa (p = 0.04, HR = 2.20, 95 % CI 1.04-4.69). Together, these data suggest that cancer-derived, alternatively spliced FN isoforms can act as prognostic indicators and that additional studies are warranted to assess the clinical utility of ED-A in BCa.

MeSH Terms (21)

Adult Aged Aged, 80 and over Alternative Splicing Area Under Curve Biomarkers, Tumor Blotting, Western Carcinoma, Transitional Cell Enzyme-Linked Immunosorbent Assay Female Fibronectins Fluorescent Antibody Technique Humans Kaplan-Meier Estimate Male Middle Aged Prognosis Protein Isoforms ROC Curve Sensitivity and Specificity Urinary Bladder Neoplasms

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