Abstract
Zinc-finger protein X-linked (ZFX) was recently identified as a novel oncoprotein in several human malignancies. In this study, we examined the correlation between ZFX expression and the clinical characteristics of stage II/III CRC patients, as well as the molecular mechanism by which ZFX apparently contributes to CRC tumor progression. Using immunohistochemistry, we detected expression of ZFX in CRC tissues collected from stage II/III patients and determined that its expression correlated with tumor differentiation and stage. Survival analysis indicated that patients with high ZFX expression had poorer overall and disease-free survival. ZFX knockdown in SW620 and SW480 CRC cells significantly inhibited cell proliferation and colony formation, enhanced apoptosis and induced cell cycle arrest. It also enhanced the sensitivity of CRC cells to 5-Fu. In a xenograft model, ZFX knockdown suppressed in vivo CRC tumor growth. Microarray analysis revealed the primary target of ZFX to be DUSP5. Whereas ZFX knockdown increased DUSP5 expression, DUSP5 knockdown rescued ZFX-mediated cell proliferation in ZFX knockdown cells. These findings demonstrate that ZFX promotes CRC progression by suppressing DUSP5 expression and suggest that ZFX is a novel prognostic biomarker and potentially useful therapeutic target in stage II/III CRC patients.
Highlights
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and second in females worldwide [1]
For stage II patients treated without postoperative chemotherapy, there was no significant correlation between Zinc-finger protein X-linked (ZFX) expression and overall survival (OS) (p = 0.825) or disease free survival (DFS) (p = 0.655) (Figure 1C)
This observation is consistent with the recent finding by Yin et al, who reported that ZFX expression is aberrantly high in tongue squamous cell carcinoma tissues and is significantly correlated with tumor grade and stage [16]
Summary
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and second in females worldwide [1]. Due to high disease heterogeneity, CRC patients at different stages experience varied outcomes and respond differently to the same therapeutic strategy, resulting in inevitable under- or over-treatment. This clinical problem appears to be more prominent in patients with stage II/III cancer, who could potentially be cured by radical surgery combined with tailored chemotherapy [6, 7]. Identification of novel molecular biomarkers, which can predict the response of antitumor therapy, could be potentially useful for prognosis assessment and therapy determination in CRC patients
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