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Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma.

ABSTRACT: Background: Recent studies have shown that the transcription factor E2F4 is involved in the progression of various tumors, but its expression and influence on immune cell infiltration and biological functions are largely unknown in hepatocellular carcinoma (HCC). Methods: The Cancer Genome Atlas (TCGA) database, the Tumor Immune Estimation Resource (TIMER) and related online tools as well as a tissue microarray (TMA) were used for analyses in our study. Results: E2F4 expression was elevated in HCC tumor tissue compared with adjacent normal tissue at both the mRNA and protein levels. Overexpression of E2F4 was markedly related to a poor prognosis in HCC patients. In addition, positively and negatively correlated significant genes of E2F4 were identified in HCC. Pathway enrichment analyses revealed that the top 100 positively correlated significant genes of E2F4 were closely related to nuclear splicing and degradation-related pathways. Furthermore, nine hub genes correlated with E2F4 expression were validated based on a protein-protein interaction (PPI) network. It was also demonstrated that E2F4 expression was negatively correlated to immune purity and positively correlated to immune cell infiltration. Conclusion: E2F4 could serve as a novel biomarker for HCC diagnosis and prognosis prediction.

SUBMITTER: Zheng Q

PROVIDER: S-EPMC7890309 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma.

Zheng Qiuxian Q Fu Qiang Q Xu Jia J Gu Xinyu X Zhou Haibo H Zhi Chen C

Journal of Cancer 20210121 6

Background: Recent studies have shown that the transcription factor E2F4 is involved in the progression of various tumors, but its expression and influence on immune cell infiltration and biological functions are largely unknown in hepatocellular carcinoma (HCC). Methods: The Cancer Genome Atlas (TCGA) database, the Tumor Immune Estimation Resource (TIMER) and related online tools as well as a tissue microarray (TMA) were used for analyses in our study. Results: E2F4 express ...[more]

PMID: 33613768

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Project description:Objective: This study aimed to validate FANCI as a potential marker for both prognosis and therapy in liver hepatocellular carcinoma. Method: FANCI expression data were acquired from GEPIA, HPA, TCGA, and GEO databases. The impact of clinicopathological features was analyzed by UALCAN. The prognosis of Liver Hepatocellular Carcinoma (LIHC) patients with highly expressed FANCI was constructed utilizing Kaplan-Meier Plotter. GEO2R was employed to identify differentially expressed genes (DEGs). Metascape was used to analyze functional pathways correlations. Protein-Protein interaction (PPI) networks were generated by Cytoscape. Furthermore, molecular complex detection (MCODE) was utilized to recognize Hub genes, which were selected to establish a prognostic model. Lastly, the relationship between FANCI and immune cell infiltration in LIHC was examined. Results: Compared to adjacent tissues, FANCI expression levels were significantly higher in LIHC tissues and were positively correlated to the cancer grade, stage, and prior hepatitis B virus (HBV) infection. High expression of FANCI was found to be associated with poor prognosis in LIHC (HR=1.89, p<0.001). DEGs that were positively correlated with FANCI were involved in various processes, including the cell cycle, VEGF pathway, immune system processes, and biogenesis of ribonucleoproteins. MCM10, TPX2, PRC1, and KIF11 were identified as key genes closely related to FANCI and poor prognosis. A reliable five-variable prognostic model was constructed with strong predictive capability. Lastly, a positive correlation was observed between FANCI expression and tumor-infiltration levels of CD8+ T cells, B cells, regulatory T (Tregs), CD4+ T helper 2 (Th2), and macrophage M2 cells. Conclusion: FANCI may hold promise as a potential biomarker for predicting prognostic outcomes, and a valuable therapeutic target for LIHC patients, with a focus on anti-proliferation, anti-chemoresistance, and combination with immunotherapy.

Project description:Purpose:Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed digestive cancers and the fourth leading cause of death worldwide. Long noncoding RNAs (lncRNAs) with key roles in HCC development and progression have emerged and are used in the diagnosis and prognostic prediction of HCC. The lncRNA gradually increased during hepatocarcinogenesis (GIHCG) is a novel lncRNA with aberrant expression in many tumors, but its prognostic value and biological role in HCC have not been fully studied. Thus, the aim of this study was to explore the expression pattern and potential biological role of GIHCG in HCC. Patients and Methods:The expression pattern of GIHCG in HCC was analyzed in our HCC cohort and validated in The Cancer Genome Atlas (TCGA) database. To assess the prognostic value of GIHCG, survival analyses and Cox regression analyses were carried out in two HCC cohorts. Functional enrichment analysis was used to predict the gene sets and pathways related to aberrant GIHCG expression. Furthermore, the relationship between GIHCG expression and immune infiltration in HCC was analyzed. Results:GIHCG was highly expressed in HCC tissues compared with normal liver tissues. In addition, high GIHCG expression was significantly correlated with inferior clinicopathological characteristics and shorter survival times. High GIHCG expression was an independent prognostic factor for overall survival and disease-free survival in the HCC cohort in our center and in the TCGA-LIHC cohort. Hallmark terms such as "G2M checkpoint", "MYC targets" and "DNA repair" were enriched in the GIHCG high-expression groups. High GIHCG expression negatively correlated with the infiltration of memory CD4+ and CD8+ T cells, natural killer cells, macrophages, dendritic cells, neutrophils and monocytes. Conclusion:The findings of our study indicate that GIHCG is a biomarker that can be used to predict the prognosis of HCC patients and is correlated with immune cell infiltration in HCC.

Project description:BackgroundAs a crucial constituent part of Polycomb repressive complex 2, PHD finger protein 19 (PHF19) plays a pivotal role in epigenetic regulation, and acts as a critical regulator of multiple pathophysiological processes. However, the exact roles of PHF19 in cancers remain enigmatic. The present research was primarily designed to provide the prognostic landscape visualizations of PHF19 in cancers, and study the correlations between PHF19 expression and immune infiltration characteristics in tumor microenvironment.MethodsRaw data in regard to PHF19 expression were extracted from TCGA and GEO data portals. We examined the expression patterns, prognostic values, mutation landscapes, and protein-protein interaction network of PHF19 in pan-cancer utilizing multiple databases, and investigated the relationship of PHF19 expression with immune infiltrates across TCGA-sequenced cancers. The R language was used to conduct KEGG and GO enrichment analyses. Besides, we built a risk-score model of hepatocellular carcinoma (HCC) and validated its prognostic classification efficiency.ResultsOn balance, PHF19 expression was significantly higher in cancers in comparison with that in noncancerous samples. Increased expression of PHF19 was detrimental to the clinical prognoses of cancer patients, especially HCC. There were significant correlations between PHF19 expression and TMB or MSI in several cancers. High PHF19 levels were critically associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that PHF19 participated in regulating carcinogenic processes including cell cycle and DNA replication, and was correlated with the progression of HCC. Intriguingly, GSEA suggested that PHF19 was correlated with the cellular components including immunoglobulin complex and T cell receptor complex in HCC. Based on PHF19-associated functional gene sets, an eleven-gene prognostic signature was constructed to predict HCC prognosis. Finally, we validated pan-cancer PHF19 expression, and its impacts on immune infiltrates in HCC.ConclusionThe epigenetic related regulator PHF19 participates in the carcinogenic progression of multiple cancers, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that PHF19 can serve as a carcinogenic indicator related to prognosis in pan-cancer, especially HCC, and shed new light on therapeutics of cancers for clinicians.

Dataset Information

Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma.

Publications

Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma.

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