Objective To investigate the common ferroptosis signature genes in two cancers based on the disease commonality between hepatocellular carcinoma and renal clear cell carcinoma. MethodsBased on the mRNA-seq data and matched clinical data of the two cancers in the GEO database and TCGA database, we used R package and part of online analysis tools to find the differentially expressed ferroptosis genes in the two cancers, and then used LASSO regression analysis to further screen the ferroptosis signature genes in the two cancers, and explored their functional characteristics and clinical significance in the two cancers based on the expression of the ferroptosis signature genes. Results Four ferroptosis genes G6PD/NRAS/CDCA3, and NDRG1 were significantly upregulated in hepatocellular carcinoma and renal clear cell carcinoma, showed good diagnostic efficacy for both cancers, and were significantly associated with patient survival prognosis. The risk model based on the four characteristic genes showed good predictive efficacy and has potential clinical application, and upregulation of NRAS expression may contribute to the pathogenesis and progression of HCC through activation of MAPK/ERK signaling pathway. Conclusions G6PD/NRAS/CDCA3, and NDRG1 are common ferroptosis signature genes for hepatocellular carcinoma and renal clear cell carcinoma, and have good diagnostic and prognostic predictive efficacy for both cancers, and upregulation of NRAS expression may contribute to the pathogenesis and progression of HCC through activation of MAPK/ERK signaling pathway.
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 explore dermatomyositis signature genes as potential biomarkers of hepatocellular carcinoma and their associated molecular regulatory mechanisms. Methods Based on the mRNA-Seq data of dermatomyositis and hepatocellular carcinoma in public databases, five dermatomyositis signature genes were screened by LASSO regression analysis and support vector machine (SVM) algorithm, and their biological functions in dermatomyositis with hepatocellular carcinoma were investigated, and a nomogram risk prediction model for hepatocellular carcinoma was constructed and its predictive efficiency was initially evaluated. The immune profile in hepatocellular carcinoma was examined based on the CIBERSORT and ssGSEA algorithms, and the correlation between five dermatomyositis signature genes and tumor immune cell infiltration and immune checkpoints in hepatocellular carcinoma was investigated. Results The expression levels of five dermatomyositis signature genes were significantly altered in hepatocellular carcinoma and showed good diagnostic efficacy for hepatocellular carcinoma, suggesting that they may be potential predictive targets for hepatocellular carcinoma, and the risk prediction model based on five dermatomyositis signature genes showed good risk prediction efficacy for hepatocellular carcinoma and has good potential for clinical application. In addition, we also found that the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through integrin-mediated activation, which in turn regulates the development and progression of hepatocellular carcinoma. Conclusion LY6E, IFITM1, GADD45A, MT1M, and SPP1 are potential predictive targets for new-onset hepatocellular carcinoma in patients with dermatomyositis, and the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through the mediation of integrins to promote the development and progression of hepatocellular carcinoma.
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.
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.
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