Clinical Characteristics and Survival Analysis of Patients With Second Primary Malignancies After Hepatocellular Carcinoma Liver Transplantation: A SEER-based Analysis.

BACKGROUND: Second primary malignancies (SPMs) after liver transplantation (LT) are becoming the leading causes of death in LT recipients. The purpose of this study was to explore prognostic factors for SPMs and to establish an overall survival nomogram. METHODS: A retrospective analysis was conducted of data from the Surveillance, Epidemiology, and End Results (SEER) database on adult patients with primary hepatocellular carcinoma who had undergone LT between 2004 and 2015. Cox regression analysis was used to explore the independent prognostic factors for SPMs. Nomogram was constructed using R software to predict the overall survival at 2, 3, and 5 years. The concordance index, calibration curves, and decision curve analysis were used to evaluate the clinical prediction model. RESULTS: Data from a total of 2078 patients were eligible, of whom 221 (10.64%) developed SPMs. A total of 221 patients were split into a training cohort (n=154) or a validation cohort (n=67) with a 7:3 ratio. The 3 most common SPMs were lung cancer, prostate cancer, and non-Hodgkin lymphoma. Age at initial diagnosis, marital status, year of diagnosis, T stage, and latency were the prognostic factors for SPMs. The C-index of the nomogram for overall survival in the training and validation cohorts were 0.713 and 0.729, respectively. CONCLUSIONS: We analyzed the clinical characteristics of SPMs and developed a precise prediction nomogram, with a good predictive performance. The nomogram we developed may help clinicians provide personalized decisions and clinical treatment for LT recipients.

Identification of methyltransferase modification genes associated with prognosis and immune features of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a malignant tumor with a high mortality rate. Methylation modifications acted a crucial role to affect cancer progression. The current study aimed to explore the potential role of methylase regulators in PAAD prognosis and immune microenvironment. METHODS: PubMed and TCGA databases were used to systematically analyze methylase regulators in PAAD. We identified three methylase clusters based on RNA methylase transcriptome data and obtained three gene clusters based on methylase modification-related differently expressed genes using principal component analysis (PCA) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) biological processes were performed to explore the processes enriched in the different subgroups and single sample gene-set enrichment analysis (ssGSEA) was used to analyze the relationship between subgroups and immune infiltration in PAAD. RESULTS: We systematically screened 43 methylase regulators in PAAD samples and identified three methylase clusters with different clinical outcomes, as well as detected a significant relationship between methylase clusters and tumor immune infiltration. The top ten mutated genes include TP53, Kirsten rat sarcoma viral oncogene homolog (KRAS), titin gene (TTN), mucin 16 (MUC16), SMAD4, cyclin-dependent kinase inhibitor 2a (CDKN2A), Ryanodine receptor isoform-1 (RYR1), ring finger 43 (RNF43), protocadherin-15 (PCDH15), and AT-rich interacting domain-containing protein 1 A gene (ARID1A). CONCLUSION: The current study constructed an m6A/m5C/m1A/m7G modulator genes and explored methylase modification-related genes, which were related to the prognosis of PAAD patients and the immune checkpoint point cytotoxic T-lymphocyte associated protein 4 (CTLA4). These findings may provide prognostic predictors and direction for immunotherapy strategies for the treatment of PAAD.

HBV induces different responses of the hepatocytes and oval cells during HBV-related hepatic cirrhosis.

Although hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC) cause a sever health problem worldwide, the underlying mechanisms are still elusive. This study aimed to investigate the responses of different cell types isolated from HBV transgenic mice. A cross-sectional set of hepatocytes and oval cells were obtained from HBV transgenic and control mice. Flow cytometry, immunohistochemistry and microarray were applied to investigate the cell biology of the hepatocytes and oval cells. Our results showed that HBV induced the proliferation of both cell oval cells and hepatocytes, and induced cell death of HBV hepatocytes while had minimal effects on oval cells. Further molecular and pathways analysis identified some genes and signaling pathways may be responsible for the different responses between oval cells and hepatocytes. In addition, analyses of selectively ten genes by IHC staining in human samples were consistent with microarray data. In summary, HBV transgenic mice is a useful model for studying the biological behaviors of oval cells affected by HBV and HBV-cirrhosis. Also, our results help better understand the mechanisms of HBV induced cirrhosis, and provide novel progenitor markers or prognostic/therapeutic markers.