Abstract
AimsThis study was designed to identify novel microRNAs (miRNAs) in plasma for detecting and monitoring hepatocellular carcinoma (HCC), independent of hepatic function and background liver diseases with different etiologies.Results(1) Four oncogenic miRNAs (miR-151, 155, 191 and 224) with high expression in HCC tissues were selected as candidates. (2) Quantitative RT-PCR using plasma samples from 107 HCC patients and 75 healthy volunteers revealed a significantly higher level of plasma miR-224 in HCC patients than in healthy volunteers according to a small-scale analysis (P < 0.0001), two independent large-scale cohort analysis (P < 0.0001, AUC 0.908). (3) miR-224 expression was significantly higher in HCC tissues and HCC cell lines than in normal hepatic tissues and fibroblasts, respectively. (P = 0.0011, 0.0150) (4) Plasma miR-224 reflected tumor dynamics; preoperative plasma levels of miR-224 were significantly reduced in postoperative samples (P = 0.0058), and plasma miR-224 levels were significantly correlated with paired miR-224 levels in HCC tissues (P = 0.0005). (5) Furthermore, plasma miR-224 levels significantly discriminated HCC patients from patients with chronic liver disease (P = 0.0008). A high plasma miR-224 level was significantly correlated with larger tumor size (P = 0.0005) and recurrences (P = 0.0027). The plasma miR-224 level could accurately detect small tumors less than 18 mm preoperatively.MethodsWe performed a systematic review of the NCBI database and selected candidate miRNAs reported as highly expressed in HCC tissue.ConclusionsPlasma miR-224 may be a sensitive biomarker for screening HCC and monitoring tumor dynamics.
Highlights
Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide
(2) Quantitative RT-PCR using plasma samples from 107 HCC patients and 75 healthy volunteers revealed a significantly higher level of plasma miR-224 in HCC patients than in healthy volunteers according to a small-scale analysis (P < 0.0001), two independent large-scale cohort analysis (P < 0.0001, AUC 0.908). (3) miR-224 expression was significantly higher in HCC tissues and HCC cell lines than in normal hepatic tissues and fibroblasts, respectively. (P = 0.0011, 0.0150) (4) Plasma miR-224 reflected tumor dynamics; preoperative plasma levels of miR-224 were significantly reduced in postoperative samples (P = 0.0058), and plasma miR-224 levels were significantly correlated with paired miR-224 levels in HCC tissues (P = 0.0005)
Plasma miR-224 may be a sensitive biomarker for screening HCC and monitoring tumor dynamics
Summary
Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Despite continuous global efforts aimed at eradication and improvements in various treatment techniques, the prognosis of HCC remains poor. Even in major advanced economies, the mortality rates have been increasing [1]. HCC is a typical viral infection-related malignancy derived from chronic hepatitis B and C [2,3], HCC has been strongly associated with lifestyle. Obesity and type 2 www.impactjournals.com/oncotarget diabetes are strongly associated with the carcinogenesis and development of HCC [4,5,6,7]. The proportion and the number of HCC patients with nonviral etiologies has been increasing on a global scale [2]
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