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Background: Repeat hepatectomy is an important treatment for patients with repeat recurrent hepatocellular carcinoma (HCC). Methods: This study was a multicenter retrospective analysis of 1,135 patients who underwent primary curative liver resection for HCC. One hundred recurrent patients with second hepatectomy were included to develop a nomogram to predict the risk of post-recurrence survival (PRS). Thirty-eight patients in another institution were used to externally validate the nomogram. Univariate and multivariate Cox regression analyses were used to identify independent risk factors of PRS. Discrimination, calibration, and the Kaplan–Meier curves were used to evaluate the model performance. Results: The nomogram was based on variables associated with PRS after HCC recurrence, including the tumor, node, and metastasis (TNM) stage; albumin and aspartate aminotransferase levels at recurrence; tumor size, site, differentiation of recurrences; and time to recurrence (TTR). The discriminative ability of the nomogram, as indicated by the C statistics (0.758 and 0.811 for training cohort and external validation cohorts, respectively), was shown, which was better than that of the TNM staging system (0.609 and 0.609, respectively). The calibration curves showed ideal agreement between the prediction and the real observations. The area under the curves (AUCs) of the training cohort and external validation cohorts were 0.843 and 0.890, respectively. The Kaplan–Meier curve of the established nomogram also performed better than those of both the TNM and the BCLC staging systems. Conclusions: We constructed a nomogram to predict PRS in patients with repeat hepatectomy (RH) after repeat recurrence of HCC. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the second most common cause of cancer-related deaths. Autophagy plays a crucial role in the development and progression of HCC. Methods: Univariate and Lasso Cox regression analyses were performed to determine a gene model that was optimal for overall survival (OS) prediction. Patients in the GSE14520 and GSE54236 datasets of the Cancer Genome Atlas (TCGA) were divided into the high-risk and low-risk groups according to established ATG models. Univariate and multivariate Cox regression analyses were used to identify risk factors for OS for the purpose of constructing nomograms. Calibration and receiver operating characteristic (ROC) curves were used to evaluate model performance. Real-time PCR was used to validate the effects of the presence or absence of an autophagy inhibitor on gene expression in HepG2 and Huh7 cell lines. Results: OS in the high-risk group was significantly shorter than that in the low-risk group. Gene set enrichment analysis (GSEA) indicated that the association between the low-risk group and autophagy- as well as immune-related pathways was significant. ULK2, PPP3CC, and NAFTC1 may play vital roles in preventing HCC progression. Furthermore, tumor environment analysis via ESTIMATION indicated that the low-risk group was associated with high immune and stromal scores. Based on EPIC prediction, CD8+ T and B cell fractions in the TCGA and GSE54236 datasets were significantly higher in the low-risk group than those in the high-risk group. Finally, based on the results of univariate and multivariate analyses three variables were selected for nomogram development. The calibration plots showed good agreement between nomogram prediction and actual observations. Inhibition of autophagy resulted in the overexpression of genes constituting the gene model in HepG2 and Huh7 cells. Conclusions: The current study determined the role played by autophagy-related genes (ATGs) in the progression of HCC and constructed a novel nomogram that predicts OS in HCC patients, through a combined analysis of TCGA and gene expression omnibus (GEO) databases. [ABSTRACT FROM AUTHOR]

In order to evaluate the epidemiology of influenza A and its surface antigens (haemagglutinin [HA] and neuraminidase [NA]) for molecular epidemiology and evolution analysis during winter 2012–2013 in Beijing, China, we worked within the framework of the Chinese National Influenza Center and collected nasal swabs of patients presenting with influenza-like illness. We found that both A(H1N1)pdm09 (46.8%) and H3N2 (53.2%) viruses were the predominant strains during the 2012–2013 influenza epidemic. The peak phase started at the second week of 2013 and lasted about 1 month. We obtained HA and NA sequences of viruses from 44 patients by using Sanger sequencing. None of the strains had the oseltamivir resistance site H274Y. Phylogenetic analysis of 29 A(H1N1)pdm09 viruses showed a genetic drift from the vaccine strain A/California/07/2009 with mutations (H155Q/R and L178I) at the antigenic sites Ca and Sa of HA; the strains were classified into genetic groups 6 and 7 because of the presence of D114N, S160G, S202T, and A214T mutations in HA. H3N2 viruses formed seasonal phylogenetic clusters representative for each season from 2000 to 2013; 15 of the 2012–2013 H3N2 strains were assigned to the A/Victoria/361/2011 genetic clade with mutations at the antigenic sites A, B and C of HA, including R158K/G, N161S, Q172H, and N294K; the 2012–2013 strains with V239I, S61N, T64I, and A214S HA mutations were classified into subgroup 3C. The mutation of potential N-linked glycosylation residues at the antigenic sites of HA and around the enzymatic active center of NA may have increased viral pathogenicity by masking antigenic sites from immune recognition. Our data suggest that influenza vaccines are generally effective, but still provide suboptimal protection due to antigenic variation. This study increases the understanding of influenza A viruses in humans and is informative for future vaccine strain selection. [ABSTRACT FROM AUTHOR]