Clinical Research Papers:
Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer
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Myung-Shin Lee1, Jisu Lee1, Joo Heon Kim2, Won Tae Kim3, Wun-Jae Kim3, Hanjong Ahn4, Jinsung Park5
1Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South Korea
2Department of Pathology, Eulji University School of Medicine, Daejeon, South Korea
3Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea
4Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
5Department of Urology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, South Korea
Jinsung Park, e-mail: [email protected]
Keywords: antibody microarray, bladder cancer, biomarkers, caldesmon, tumor progression
Received: June 21, 2015 Accepted: September 15, 2015 Published: September 25, 2015
The expression and function of caldesmon (CAD) in urothelial bladder carcinoma (BC) have not been reported. Here, we investigated the expression, prognostic value, and potential functional mechanism of CAD in primary non-muscle-invasive bladder cancer (NMIBC). Protein profiling of tissue samples using antibody microarrays showed significantly higher CAD expression in muscle-invasive BC tissues compared with NMIBC tissues. We then validated the CAD expression in BC cells by immunohistochemistry analysis using paraffin-embedded tissue blocks and western blots using BC cell lines. In addition, we examined the expression of CAD variants by reverse transcription-polymerase chain reaction, and confirmed the expression of low-molecular-weight isoforms (L-CAD), specifically encoded by WI-38 L-CAD II (transcript variant 2), in BC cells. Survival analysis in an independent primary NMIBC cohort comprising 132 patients showed that positive CAD expression was significantly associated with poorer prognosis than no CAD expression with regard to recurrence- and progression-free survival (p = 0.001 and 0.014, respectively). Multivariate analyses further indicated that positive CAD expression was an independent predictor of progression-free survival (p = 0.032; HR = 5.983). Data obtained from in vitro silencing and overexpression studies indicated that L-CAD promotes migration and invasiveness of BC cells. Immunofluorescence assays showed dramatic structural changes in the actin cytoskeleton of BC cells after L-CAD overexpression. Our findings collectively suggest that L-CAD overexpression in primary NMIBC is significantly associated with tumor progression and that a possible mechanism for L-CAD's activity is implicated in increased cell motility and invasive characteristics through morphological changes in BC cells.
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