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BackgroundThe COVID-19 pandemic has spread rapidly across the globe. Cancer patients have a higher risk of severe infections and associated mortality than the general population. However, the lethal effect of Omicron-variant affection on advanced pancreatic and biliary cancer patients is still not clear. Herein, we designed an observational study to shed light on the influence of the Omicron variant on this so-called “King of Cancer” and improve management of these patients with COVID-19 in the future.MethodsOmicron-infected patients with advanced pancreatic and biliary cancer were enrolled from 15 April to 31 May 2022. Four groups were set up in this study: Group 1, Omicron-infected cancer patients (N = 4); Group 2, non-infected cancer patients (N = 4); Group 3, infected non-cancer-afflicted subjects (N = 4); Group 4, non-infected non-cancer-afflicted subjects (N = 4). On Days 0, 7, and 14 after infection, the blood samples were collected dynamically from all subjects. The primary endpoints were disease severity and survival.ResultsAt the endpoint of this observational study, Patient Nos. 2, 3, and 4 died separately on Days 11, 25, and 13 after viral infection. All of them had advanced cancer, with a death rate of up to 75%. Group 1 presented an overall T-cell exhaustion status compared with other groups. Group 1 had obviously lower T-cell populations and higher B-cell percentages and CD4+T/CD8+T ratios (P ConclusionsAdvanced pancreatic and biliary cancer patients with Omicron infection have severe symptoms and poor outcomes. More attention, protective measures, and routine healthcare services should be recommended to these vulnerable populations in clinical practice during the pandemic in the foreseeable future.

Background With the advancement of hepatocellular carcinoma (HCC) treatment technology, the treatment options for HCC patients have increased. However, due to high heterogeneity, among other reasons, the five-year survival rate of patients is still very low. Currently, gene expression prognostic models can suggest more appropriate strategies for the treatment of HCC. This study investigates the role of FAT10 in hepatocarcinogenesis and its underlying mechanism. Methods The expression of FAT10 was detected by immunohistochemical method using tissue arrays containing 4 specimens of patients with digestive cancer. The expression of FAT10 was determined by a tissue microarray which included 286 pairs of HCC samples and corresponding normal mucosae and was further confirmed by real-time polymerase chain reaction (PCR) and western blot. The Kaplan-Meier survival curve was used to determine the correlation of FAT10 expression with patients' recurrence and overall survival (OS) rate. In vivo, liver fibrosis, cirrhosis, and HCC models were established to assess the FAT10 expression. Moreover, FAT10 over-expressing cell lines were used to determine the molecular mechanism underlying the FAT10-induced cell proliferation and hepatocarcinogenesis by reporter gene measure, real-time PCR, and western blot. Based on TCGA database, signal pathways associated with FAT10 and HCC invasion and metastasis were analyzed by KEGG enrichment analyze. Results Overexpression of FAT10 in HCC was observed in this study compared with its expression in other digestive tumors. Clinicopathological analysis revealed that FAT10 expression levels were closely associated with tumor diameters and poor prognosis of HCC. This study also confirmed through in vivo experiments that the expression of FAT10 in liver fibrosis, cirrhosis, and HCC gradually increases. Further study revealed that forced FAT10 expression enhanced the growth ability of HCC cells and mediated the degradation of the critical anti-cancer protein p53, which led to carcinogenesis. Finally, 9 signal pathways related to HCC metastasis were obtained through bioinformatics analysis. Conclusions FAT10 may act as a proto-oncogene that facilitates HCC carcinogenesis by mediating p53 degradation, and the expression of FAT10 is negatively correlated with the prognosis of HCC patients. FAT10 is expected to become a potential combined target and prognostic warning marker for HCC treatment.

MicroRNAs (miRNAs) are involved in tumorigenesis, progression, recurrence, and drug resistance of hepatocellular carcinoma (HCC). However, few miRNAs have been identified and entered clinical practice. Herein, we report that microRNA (miR)-552 is upregulated in HCC tissues and has an important function in liver tumor-initiating cells (T-ICs). Functional studies revealed that a forced expression of miR-552 promotes liver T-IC self-renewal and tumorigenesis. Conversely, miR-552 knockdown inhibits liver T-IC self-renewal and tumorigenesis. Mechanistically, miR-552 downregulates phosphatase and tensin homolog (PTEN) via its mRNA 3′ UTR and activates protein kinase B (AKT) phosphorylation. Our clinical investigations elucidated the prognostic value of miR-552 in HCC patients. Furthermore, miR-552 expression determines the responses of hepatoma cells to sorafenib treatment. The analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrated that miR-552 may predict sorafenib benefits in HCC patients. In conclusion, our findings revealed the crucial role of the miR-552 in liver T-IC expansion and sorafenib response, rendering miR-552 an optimal target for the prevention and intervention in HCC.

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and heterogeneity. Genetic mutations caused by driver genes are important contributors to the formation of the tumor microenvironment. The purpose of this study is to discuss the expression of cancer driver genes in tumor tissues and their clinical value in predicting the prognosis of HCC.Methods: All data were sourced from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) public databases. Differentially expressed and prognostic genes were screened by the expression distribution of the cancer driver genes and their relationship with survival. Candidate genes were subjected to functional enrichment and transcription factor regulatory network. We further constructed a prognostic signature and analyzed the survival outcomes and immune status between different risk groups.Results: Most cancer driver genes are specifically expressed in cancer tissues. Driver genes may influence HCC progression through processes such as transcription, cell cycle, and T-cell receptor-related pathways. Patients in different risk groups had significant survival differences (p < 0.05), and risk scores showed high predictive efficacy (AUC>0.69). Besides, risk subgroups were also associated with multiple immune functions and immune cell content.Conclusion: We confirmed the critical role of cancer driver genes in mediating HCC progression and the immune microenvironment. Risk subgroups contribute to the assessment of prognostic value in different patients and explain the heterogeneity of HCC.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. MiR-371 has recently emerged as an important regulator in tumorigenesis, and may serve as a biomarker for malignant tumors. We transfected miR-371 or its inhibitor in two human HCC cell lines, then used 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, soft agar colony formation, and transwell migration assays to evaluate the effects on cell proliferation, migration, and invasion. We found that miR-371 was positively correlated with HCC metastasis and poor prognosis in the inflicted patients, and the high expression of miR-371 was promoted, whereas a low level of miR-371 depressed cell proliferation and invasion. We found PTEN to be a direct target of miR-371. The overexpression or knockdown of PTEN exhibited the opposite effects from those of miR-371 on cell proliferation and migration. Our study demonstrates that miR-371 promotes proliferation and metastasis in HCC by targeting PTEN. [BMB Reports 2019; 52(5): 312-317].

Background The effective evaluation of cholangiocarcinoma (CCA) is challenging due to a lack of accurate screening tools. Consequently, there is an urgent need to screen out effective biomarkers. Bioinformatics analysis on a substantial amount of transcriptomic data to screen biomolecules allows for the verification of histological samples, and can provide a new method for CCA biomolecule screening in diagnosis and prognosis. Methods EdgeR model was used to analyze The Cancer Genome Atlas (TCGA)-extracted CCA data set, and to determine the differential expression of mRNAs. Based on this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to perform functional and pathway enrichment analysis. Subsequently, a protein interaction network was also established to identify the key differential node genes. Then, the previously determined differential genes were analyzed to establish a link between these genes and clinical prognosis. Finally, we used tissue samples to realize our results via IHC, Western blot and qRT-PCR. Results A total of 5,561 differential mRNAs were screened, including 3,473 upregulated genes and 2,088 downregulated genes. GO and KEGG enrichment analysis showed that the upregulated genes had significantly enriched cell adhesion, concentrated chromosomal motility, and microtubule motility. Downregulated genes were significantly enriched in heterologous metabolism and exosomes. Furthermore, we found upregulated genes were significantly enriched in the cancer pathways and cell cycle. Downregulated genes were enriched in the metabolic pathways and biosynthesis of antibiotics. Ten hub genes were screened out through the protein interaction network; among these, the AURKB and PLK1 genes were closely related to the clinical prognosis of patients. Results of the immunohistochemical staining, Western blot and qRT-PCR all showed that the expression of AURKB and PLK1 in cancer tissues was higher than that in the adjacent tissues, and this difference was statistically significant (P