A novel signature constructed by super-enhancer-related genes for the prediction of prognosis in hepatocellular carcinoma and associated with immune infiltration.

Background: Super-enhancer (SE) refers to a regulatory element with super transcriptional activity, which can enrich transcription factors and drive gene expression. SE-related genes play an important role in the pathogenesis of malignant tumors, including hepatocellular carcinoma (HCC). Methods: The SE-related genes were obtained from the human super-enhancer database (SEdb). Data from the transcriptome analysis and related clinical information with HCC were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. The upregulated SE-related genes from TCGA-LIHC were identified by the DESeq2R package. Multivariate Cox regression analysis was used to construct a four-gene prognostic signature. According to the median risk score, HCC patients were divided into high-risk and low-risk group patients. Results: The Kaplan-Meier (KM) curve showed that a significantly worse prognosis was found for the high-risk group (P<0.001). In the TCGA-LIHC dataset, the area under the curve (AUC) values were 0.737, 0.662, and 0.667 for the model predicting overall survival (OS) over 1-, 3-, and 5- years, respectively, indicating the good prediction ability of our prediction model. This model's prognostic value was further validated in the LIRI-JP dataset and HCC samples (n=65). Furthermore, we found that higher infiltration level of M0 macrophages and upregulated of CTLA4 and PD1 in the high-risk group, implying that immunotherapy could be effective for those patients. Conclusion: These results provide further evidence that the unique SE-related gene model could accurately predict the prognosis of HCC.

Diagnostic Value of CD4/CD8 in Scrub Typhus.

Scrub typhus is often misdiagnosed in febrile patients, leading to antibiotic abuse and multiple complications. We conducted a retrospective record review at the Fourth Affiliated Hospital of Guangxi Medical University in China. Data were collected on 52 patients with a confirmed diagnosis of scrub typhus and complete clinical data. In addition, data were collected on 52 patients with bloodstream infection, 25 patients with HIV infection, 112 patients with common community-acquired pneumonia (CCAP), and 36 patients with severe community-acquired pneumonia (SCAP) to serve as control groups. The peripheral blood CD4 and CD8 counts, CD4/CD8 ratio, C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, creatinine, and ß2 microglobulin levels; and the white blood cell count and neutrophil percentage were compared between the scrub typhus and the control groups. The value of these biomarkers in the diagnosis of scrub typhus was assessed using receiver-operating characteristic curve analysis. The scrub typhus group had a significantly lower CD4 count and CD4/CD8 ratio than the bloodstream infection, CCAP, and SCAP groups, and a significantly greater CD4 count and CD4/CD8 ratio than the HIV infection group. In contrast, the scrub typhus group had a significantly greater CD8 count than the bloodstream infection and CCAP and SCAP groups, and it had a lower level of CD8 than the HIV infection group. The areas under the curve of CD4/CD8 were more than 0.93 in the receiver-operating characteristic curve analysis. These findings suggest that the CD4/CD8 ratio is a useful ancillary test for diagnosing scrub typhus.

Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation.

miRNAs play an indispensable role in human carcinogenesis. Dysregulated miR-1180-3p has been observed in several types of cancer, including hepatocellular carcinoma (HCC). This study intends to correlate the expression level of miR-1180-3p with clinical features and overall survival in HCC patients. The expression and clinical significance of miR-1180-3p, selected from GEO and TCGA databases, were verified using an RT-qPCR method. The target genes of miR-1180-3p were obtained using 3 miRNA target gene prediction databases, and their functions were analyzed using the online tool WebGestalt. miR-1180-3p expression was significantly upregulated in 88 HCC tissues compared with non-tumor liver tissues (0.004 ± 0.009 vs. 0.002 ± 0.002, t = - 2.099, P = 0.038). Additionally, we found that the expression levels of miR-1180-3p were significantly correlated with tumor number (χ2 = 9.157, P = 0.006) and MVI (χ2 = 11.354, P = 0.003). Based on Kaplan-Meier analysis, patients with high miR-1180 expression had a shorter overall survival than those with low miR-1180-3p expression (P = 0.002). Furthermore, multivariate Cox analyses indicated that miR-1180-3p expression was an independent prognostic factor for overall survival (HR = 13.36, 95% CI 1.16, 153.69, P = 0.038). In addition, a total of 733 target genes of miR-1180-3p were found from three prediction databases. The GO analyses demonstrated that the target genes were closely related to the proliferation and malignancy of tumors. The KEGG analysis showed that target genes were enriched in several key cancer-related signaling pathways, including the Pathways in cancer, the Ras signaling pathway, and the MAPK signaling pathway. In conclusion, we demonstrate that miR-1180-3p is upregulated in HCC and is associated with a poor prognosis. Thus, miR-1180-3p might be useful as a prognostic marker for HCC.