Clinical significance ofmicroRNA-148ain patients with early relapse of stage II stage and III colorectal cancer after curative resection


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Abstract

Development of robust prognostic/predictive biomarkers in patients with colorectal cancer (CRC) is imperative for advancing treatment strategies for this disease. We aimed to determine whether expression status of microRNAs might be a simple and reliable biomarker to detect postoperative early relapse in patients with CRC after radical resection. We used microRNA arrays and identified thatmicroRNA-148a(miRNA-148a) had substantially different expression levels in early and nonearly relapsed stage II and III CRC tissues. The validation study, which included 55 early relapsed patients and 55 nonearly relapsed patients, further confirmed overexpression ofmiRNA-148ain nonearly relapsed samples. Subsequently, we explored whether the serum level ofmiRNA-148acan be used to predict early CRC recurrence. Thein vitroandin vivoeffects ofmiRNA-148awere examined by cell proliferation, migration, and invasion, as well as cell cycles, and xenograft in null mice. Last,miRNA-148awas investigated as a potential biomarker for identifying early relapse. Cellular studies demonstrated that the overexpression ofmiRNA-148ainhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed thatmiRNA-148acaused an accumulation of the G2 population. Moreover, lower levels ofmiRNA-148aexpression were associated with significantly shorter disease-free survival rates and poorer overall survival rates. This study showed thatmiRNA-148acan inhibit tumorigenesis and reduce the early recurrence of CRC. These findings suggest thatmiRNA-148amay have potential clinical applications for predicting the early relapse of patients with CRC after radical resection.

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