Background: Numerous genetic sequencing projects have demonstrated that alterations in Polε (DNA polymerase epsilon ) due to various causes are associated with the development of multiple human cancers. However, the biological functions of its four core genes, POLE1/2/3/4/, in the occurrence, progression, and prognosis of hepatocellular carcinoma(HCC) remain poorly understood to date. Methods: Multi-omics, multi-level deep mining of HCC data from TCGA and other publicly available databases by using online analysis tools from GEPIA2, TIMER2.0, DAVID, Kaplan-Meier plotter, cBioPortal and MethSurv databases, as well asthe R package to assess Polε family members in HCC for their potential biological functions. Results: We found that the four target genes were significantly upregulated in HCC (P<0.001), their high expression was associated with a lower survival rate (P<0.05), and both diagnostic ROC curves and disease-specific survival time-dependent ROC curves suggested that POLE2/3 showed better disease predictive efficacy, and the four genes were significantly associated with immune infiltration, and drug sensitivity analysis suggested that the high expression groups of four target genes showed higher drug sensitivity in some chemotherapeutic drugs(P<0.001). Conclusion: The POLE1/2/3/4are potential prognostic predictive molecules for HCC and correlate with immune infiltration,and high expression of POLE may serve as a potential predictor of the effect of targeted therapies. POLE2/3 may be the potential diagnostic biomarkers for HCC, and the expression level of POLE3 may serve as a biological predictive target for HCC chemotherapy sensitivity.

Objective To investigate the effect of COVID-19 infection on pancreatic cancer . Methods Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. And the above procedures were performed in R software. Results The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases, and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes, and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. Conclusion The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promotes the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

Objective To investigate the activation of hepatic embryonic stem cell factor in hepatocellular carcinoma and its characteristic effect on hepatocellular carcinoma. Methods Based on mRNA-seq data of hepatocellular carcinoma and matched clinical data in the TCGA database, and mRNA-seq data of hepatic embryonic stem cell genes screened by laboratory sequencing, we used the R package and some online analysis tools to find activated hepatic embryonic stem cell genes in hepatocellular carcinoma, and used support vector machine (SVM) and LASSO regression analysis to further screen out significantly differentially expressed hepatic embryonic stem cell genes, and to investigate their functional characteristics and clinical significance in hepatocellular carcinoma based on the expression of these hepatic embryonic stem cell genes. Finally, the expression of five embryonic stem cell factors in HCC tissues was detected based on immunohistochemical methods. Results Five liver embryonic stem cell genes, TYW3/CKLF/P2RY6/TUBA1B and RSU1 were significantly upregulated in hepatocellular carcinoma, showed good diagnostic efficacy for hepatocellular carcinoma, and were significantly associated with a poorer survival prognosis of patients. The prognostic model based on the five hepatic embryonic cell genes showed good predictive efficacy and has good potential for clinical application, immunohistochemical expression validation results also showed high expression of TYW3/CKLF/P2RY6/TUBA1B, and RSU1 in HCC, and were highly expressed in HCC and mainly expressed in the cytoplasm. Conclusion The activation of five hepatic germ cell genes, TYW3/CKLF/P2RY6/TUBA1B, and RSU1 are important diagnostic targets and prognostic markers for hepatocellular carcinoma, which significantly correlated with patient clinical prognosis. And the prognostic model of HCC based on TYW3/CKLF/P2RY6/TUBA1B, and RSU1 has a good clinical application potential for hepatocellular carcinoma.

BACKGROUND Numerous genetic sequencing projects have demonstrated that alterations in Polε (DNA polymerase epsilon ) due to various causes are associated with the development of multiple human cancers. However, the biological functions of its four core genes, POLE1/2/3/4/, in the occurrence, progression, and prognosis of hepatocellular carcinoma(HCC) remain poorly understood to date. METHODS Multi-omics, multi-level deep mining of HCC data from TCGA and other publicly available databases by using online analysis tools from GEPIA2, TIMER2.0, DAVID, Kaplan-Meier plotter, cBioPortal and MethSurv databases, as well as the R package to assess Polε family members in HCC for their potential biological functions. RESULTS We found that the four target genes were significantly upregulated in HCC (P < 0.001), their high expression was associated with a lower survival rate (P < 0.05), and both diagnostic ROC curves and disease-specific survival time-dependent ROC curves suggested that POLE2/3 showed better disease predictive efficacy, and the four genes were significantly associated with immune infiltration, and drug sensitivity analysis suggested that the high expression groups showed higher drug sensitivity in some chemotherapeutic drugs(P < 0.001). CONCLUSIONS The POLE1/2/3 are potential prognostic predictive molecules for HCC and correlate with immune infiltration, and high expression of POLE may serve as a potential predictor of the effect of targeted therapies. POLE2/3 may be the potential diagnostic biomarkers for HCC, and the expression level of POLE3 may be a biological predictor of HCC chemotherapy sensitivity.

Objective To investigate whether there is an association between immune abnormalities and hepatocellular carcinogenesis in patients with the autoimmune disease systemic lupus erythematosus (SLE), and to explore the possible mechanisms of the association. Methods Based on the mRNA-Seq data of SLE and hepatocellular carcinoma in the public database, we screened the differentially expressed genes using GEO2R, R "Limm" package, and weighted gene co-expression network analysis (WGCNA), respectively, and used random forest tree algorithm to screen out the common genes in both diseases. A random forest(RF) tree algorithm was used to screen out the common genes in the two diseases, to investigate the biological functions of the genes in hepatocellular carcinoma, to construct a nomogram risk prediction model for hepatocellular carcinoma, and to evaluate the predictive efficiency of the model. The immune profile in hepatocellular carcinoma was evaluated based on CIBERSORT and ssGSEA algorithms, and the association of signature genes with the level of tumor immune cell infiltration and the correlation of immune checkpoints in hepatocellular carcinoma were also explored. Results The expression levels of 2 SLE signature genes, CCNB2 and TOP2A, were significantly upregulated in hepatocellular carcinoma, and showed good diagnostic efficacy and clinical prognostic efficacy for hepatocellular carcinoma, suggesting that they may be potential biological targets for hepatocellular carcinoma, and the hepatocellular carcinoma risk prediction model based on the expression levels of CCNB2 and TOP2A showed good risk prediction for hepatocellular carcinoma and has good potential for clinical application. In addition, it was found that the up-regulation of CCNB2 expression may accelerate the G2/M transition of the hepatocellular carcinoma cell cycle, inhibit the apoptotic process, and promote the rate of tumor cell appreciation through the mediation of the p53 signaling pathway, thus contributing to the development and progression of hepatocellular carcinoma. Conclusion The SLE signature genes CCNB2 and TOP2A are potential predictive targets for new-onset hepatocellular carcinoma in SLE patients, and the upregulation of CCNB2 expression may promote hepatocellular carcinoma development and progression through the mediation of the p53 signaling pathway.