MicroRNAs (miRNAs) have been demonstrated to play critical roles in regulating cancer cell proliferation, survival and sensitivity to chemotherapy. The potential application of using miRNAs to predict therapeutic response to cancer treatment holds high promise but miRNAs with predictive value remain to be identified and underlying mechanisms have not been completely understood. Here, we show a strong correlation between miR-621 expression and chemosensitivity to paclitaxel plus carboplatin (PTX/CBP) regimen, an effective neoadjuvant chemotherapy for breast cancer patients. High level of miR-621 predicts better response to PTX/CBP regimen neoadjuvant chemotherapy in breast cancer patients, who also tend to achieve pathological complete response. Ectopic overexpression of miR-621 promoted apoptosis and increased chemosensitivity to paclitaxel and carboplatin both in cultured breast cancer cells and in xenograft tumor model. We further show that FBXO11 is a direct functional target of miR-621 and miR-621 level is negatively correlated with FBXO11 expression in breast cancer patients. Ectopic expression of FBXO11 attenuated increased apoptosis in breast cancer cells overexpressing miR-621 upon PTX or CBP treatment. Consistently, high FBXO11 expression significantly correlated with poor survival in breast cancer patients. Mechanistically, we found in breast cancer cells FBXO11 interacts with p53 and promotes its neddylation, which suppressed p53 transactivity. Accordingly, miR-621-dependent FBXO11 suppression enhanced p53 activity and increased apoptosis in breast cancer cells exposed to chemotherapeutics. Taken together, our data suggest that miR-621 enhances chemosensitivity of breast cancer cells to PTX/CBP chemotherapy by suppressing FBXO11-depedent inhibition of p53. miR-621 may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment.

The proposed nomogram with neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio resulted in accurate prognostic prediction for decompensated cirrhotic patients without ACLF.

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Steatosis could affect liver stiffness measurement in patients with nonalcoholic fatty liver disease and chronic hepatitis C. In this study, we aimed to investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)-infected patients and develop a diagnostic algorithm for prediction of liver fibrosis by liver stiffness based on the controlled attenuation parameter. A total of 488 HBV-infected patients who underwent clinical examination, Fibroscan and liver biopsy were prospectively enrolled. The best liver stiffness measurement (kPa) cut-offs for significant fibrosis (S≥3) and advanced fibrosis (S≥4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter cut-off for severe steatosis (≥30%) was 287 dB/m. Among patients with low-grade fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in subjects with severe steatosis or controlled attenuation parameter ≥287 dB/m compared with those without. Moreover, in subjects with low-grade fibrosis, a higher rate of false-positive rate was observed in patients with severe steatosis than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and in patients with CAP≥287 dB/m compared with their counterpart (F0-F2: 23.7% vs 9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by γ-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of 0.17. In patients with GPR<0.17, similar results were observed. The presence of steatosis may lead to overestimation of fibrosis assessed by liver stiffness measurement in patient with chronic hepatitis B. A diagnostic algorithm for assessing fibrosis using liver stiffness was developed by combining both controlled attenuation parameter and GPR values.