Radiofrequency ablation (RFA) is recommended as a first-line therapy for small hepatocellular carcinoma (HCC). Tumor location is a potential factor influencing the procedure of RFA. To compare oncologic outcomes of RFA for different tumor locations, this retrospective study enrolled 194 patients with small HCC who had undertaken RFA. The HCC nodules were classified as peri-hepatic-vein (pHV) or non-pHV, peri-portal-vein (pPV) or non-pPV, and subcapsular or non-subcapsular HCC. The regional recurrence-free survival (rRFS), overall survival (OS), recurrence-free survival (recurrence in any location, RFS) and distant recurrence-free survival (dRFS) were compared. Operation failures were recorded in five pPV HCC patients, which was more frequent than in non-pPV HCC patients (p = 0.041). The 1-, 3-, and 5-year rRFS was 68.7%, 53.7%, and 53.7% for pHV patients and 85.1%, 76.1%, and 71.9% for non-pHV patients, respectively (p = 0.012). After propensity score matching, the 1-, 3-, and 5-year rRFS was still worse than that of non-pHV patients (p = 0.013). The OS, RFS, and dRFS were not significantly different between groups. Conclusions: A pHV location was a risk factor for the regional recurrence after RFA in small HCC patients. The tumor location may not influence OS, RFS, and dRFS. Additionally, a pPV location was a potential high-risk factor for incomplete ablation.

Osteosarcoma (OS) is a malignant bone cancer with severe chromosomal abnormalities and genetic aberrations. Our previous work reported the dedifferentiation of OS, which is related to poor prognosis. However, the molecular mechanism that regulates OS dedifferentiation is still a subject of exploration. Emerging evidence has suggested that microRNAs (miRNAs) are associated with the pathogenesis of OS and could potentially be developed for use as diagnostic biomarkers and therapeutic strategies. In the present study, we intended to illustrate the role of miR-34a in the dedifferentiation of OS. Upregulation of miR-34a was observed while OS cells were induced into stem-like phenotype. Notably, inhibition of miR-34a could promote the reprogramming transition of OS. Further exploration on the downstream network of miR-34a identified that blocking plasminogen activator inhibitor-1 (PAI-1) expression could restrain OS dedifferentiation into cancer stem-like cells by downregulating SRY-related-HMG box (Sox) 2. We also showed that Sox2 overexpression rescued the suppression phenotype driven by PAI-1 inhibition. Conversely, PAI-1 inhibitor (PAI-039) could suppress the upregulation of Sox2 expression caused by miR-34a inhibition. Be applying bone extracellular matrix (BEM)-OS models, we demonstrated the phenotypic heterogeneity of OS cells, consistent with a strong concordance between PAI-1 and Sox2 expression levels. Taken together, our findings proved miR-34a to be a bona fide suppressor involved in the regulation of OS dedifferentiation. Targeting miR-34a or its direct target PAI-1 could offer new strategies for OS treatment.

Background and AimThe existed staging systems were limited in the accuracy of prediction for overall survival (OS) of hepatocellular carcinoma (HCC) patients. The aim of this study is to establish a novel inflammation‐based prognostic system with nomogram for HCC patients.MethodsA prospective cohort of patients was recruited and assigned to the training cohort (n = 659) and validation cohort (n = 320) randomly. Different inflammation‐based score systems were evaluated to select the best one predicting overall survival (OS). The inflammation‐based score system with the highest predicting value and the parameters best reflecting tumor burden identified by multivariate analysis were selected to construct a novel predicting nomogram system. The predictive accuracy and discriminative ability of the nomogram were evaluated by concordance index (C‐index) and calibration curve and compared with conventional staging systems.ResultsWith a highest C‐index and areas under the receiver operating characteristic curve (AUC), C‐reactive protein/albumin ratio (CAR) was selected to construct the novel system, along with tumor number, tumor size, macrovascular invasion and extra‐hepatic metastases. The C‐index of the nomogram was 0.813 (95% CI, 0.789‐0.837) in the training cohort and 0.794 (95% CI, 0.756‐0.832) in the validation cohort. The calibration curve for predicting probability of survival showed that the nomogram had a high consistency with follow‐up data. The C‐index of the novel system was higher than other conventional staging systems (P < 0.001).ConclusionsThe novel inflammation‐based nomogram, developed from prospectively collected data in the present study, predicted the OS of HCC patients.

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Background: There is not yet an effective marker in predicting the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC) patients. The Gustave Roussy Immune Score (GRIm-Score) based on three objective variables, namely, neutrophil-to-lymphocyte ratio (NLR), serum albumin level (ALB), and lactate dehydrogenase (LDH), was developed as feasible prognostic indication in lung cancer patients receiving ICIs therapies. Our study aimed to adapt the GRIm-Score (HCC-GRIm-Score) in HCC patients who received ICIs therapies and thus improving the predictive ability.Methods: From January 2018 to September 2020, 261 patients who received ICIs therapy were retrospectively included and divided into training and validation groups. After determining the factors for HCC-GRIm-Score by multivariable analysis from training group, the optimized HCC-GRIm-Score was validated and compared to the original GRIm-Score and the Barcelona clinic liver cancer (BCLC) staging system.Results: One hundred sixty-one and 80 patients were assigned into the training and validation groups, respectively. Two more factors, aspartate transaminase-to-alanine transaminase ratio [hazard ratio (HR), 1.51; 95% confidence interval (CI), 0.94–2.42] and total bilirubin (HR, 1.76; 95% CI, 1.07–2.88), were identified as independent prognostic factors for overall survival (OS) and integrated in the HCC-GRIm-Score system according to the multivariable analysis. A risk score based on the HCC-GRIm-Score indicated that patients presenting high score (&gt;2) suffered from significantly shorter median OS of 10.3 months compared to those with a low score (not reached; HR, 2.99; 95% CI, 1.89–4.75; p &lt; 0.001). In the validation group of 80 patients, the patients presenting a high score showed an inferior OS (HR 5.62, 95% CI, 1.25–25.24; p = 0.024). HCC-GRIm-Score had the highest area under curve of 0.719 (95% CI, 0.661–0.773) compared to original GRIm-Score and BCLC staging system.Conclusion: The present study confirmed that the modified HCC-GRIm-Score system provided superior predictive ability in identifying the HCC patients potentially benefit from ICIs therapies, compared to the original GRIm-Score and the BCLC staging system.