scholarly journals Comprehensive Pan-Cancer Genomic Analysis Reveals PHF19 as a Carcinogenic Indicator Related to Immune Infiltration and Prognosis of Hepatocellular Carcinoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Zheng-yi Zhu ◽  
Ning Tang ◽  
Ming-fu Wang ◽  
Jing-chao Zhou ◽  
Jing-lin Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Expression Patterns ◽  
Genomic Analysis ◽  
Interaction Network ◽  
Suppressor Cells ◽  
Cell Receptor ◽  
Phd Finger ◽  
Immune Infiltration ◽  
Pan Cancer

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.

scholarly journals Bioinformatic Evidence Reveals that Cell Cycle Correlated Genes Drive the Communication between Tumor Cells and the Tumor Microenvironment and Impact the Outcomes of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Dongdong Chen ◽  
Zhijun Feng ◽  
Mingzhen Zhou ◽  
Zhijian Ren ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Poor Prognosis ◽  
Interaction Network ◽  
Prognostic Biomarkers ◽  
Cancer Type ◽  
Hematopoietic Stem ◽  
Key Genes

Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein–protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan–Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes’ expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.

scholarly journals MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Huahui Li ◽  
Yuting Li ◽  
Ying Zhang ◽  
Binbin Tan ◽  
Tuxiong Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Transmembrane Protein ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Mapk Signaling ◽  
Receptor Interaction ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Pathway Analyses

Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine–cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein–protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.

scholarly journals TCGA Pan-Cancer genomic analysis of Alternative Lengthening of Telomeres (ALT) related genes

2020 ◽  
Author(s):  
Isaac Armendáriz-Castillo ◽  
Andrés López-Cortés ◽  
Jennyfer García-Cárdenas ◽  
Patricia Guevara-Ramírez ◽  
Paola E. Leone ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Genomic Analysis ◽  
Interaction Network ◽  
Telomere Maintenance ◽  
The Cancer Genome Atlas ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening ◽  
Pan Cancer

AbstractTelomere maintenance mechanisms (TMM) are used by cancer cells to avoid apoptosis, 85-90% reactivate telomerase, while 10-15% use the alternative lengthening of telomeres (ALT). Due to anti-telomerase-based treatments, some tumors have the ability to switch from a telomerase-dependent mechanism to ALT, in fact, the co-existence between telomerase and the ALT pathway have been observed in a variety of cancer types. Despite different elements in the ALT pathway have been uncovered, the molecular mechanism and other factors are still poorly understood, which difficult the detection and treatment of ALT-positive cells, which are known to present poor prognosis. Therefore, with the aim to identify potential molecular markers to be used in the study of ALT, we combined simplistic in silico approaches in 411 telomere maintenance (TM) genes which have been previously validated or predicted to be involved in the ALT pathway. In consequence, we conducted a genomic analysis of these genes in 31 Pan-Cancer Atlas studies (n=9,282) from The Cancer Genome Atlas in the cBioPortal and found 325,936 genomic alterations, being mRNA high and low the top alterations with 65,.8% and 10.7% respectively. Moreover, we analyzed the highest frequency means of genomics alterations, identified and proposed 20 genes, which are highly mutated and up and down regulated in the cancer studies and could be used for future analysis in the study of ALT. Finally, we made a protein-protein interaction network and enrichment analysis to obtain an insight into the main pathways these genes are involved. We could observe their role in main processes related to the ALT mechanism like homologous recombination, homology directed repair (HDR), HDR through homologous recombination and telomere maintenance and organization.. Overall, due to the lack of understanding of the molecular mechanisms and detection of ALT-positive cancers, we identified and proposed more molecular targets that can be used for expression analysis and additional ex vivo assays to validate them as new potential therapeutic markers in the study of the ALT mechanism.

scholarly journals Prognostic and immunological role of Fam20C in pan-cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Xinpeng Liu ◽  
Yuanbo Zhan ◽  
Wenxia Xu ◽  
Xiaoyao Liu ◽  
Yawei Geng ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Sequence Similarity ◽  
Expression Patterns ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Tumor Cell Migration ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Pan Cancer

Abstract Background: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration. Methods: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan–Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma). Results: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2–T4 and stages N0–N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD. Conclusion: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.

scholarly journals PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingxia Deng ◽  
Long Peng ◽  
Jiamin Li ◽  
Xiong Liu ◽  
Xichun Xia ◽  
...  
Keyword(s):  
Survival Rates ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Myeloid Derived Suppressor Cell ◽  
Tumor Tissues ◽  
Tumor Types ◽  
The Relationship ◽  
Pan Cancer

Recent studies have shown that PPP1R14B was highly expressed in tumor tissues and patients with high expression of PPP1R14B had poor survival rates. However, the function and mechanisms of PPP1R14B in tumor progression remain ill defined. There was also lack of pan-cancer evidence for the relationship between PPP1R14B and various tumor types based on abundant clinical data. We used the TCGA project and GEO databases to perform pan-cancer analysis of PPP1R14B, including expression differences, correlations between expression levels and survival, genetic alteration, immune infiltration, and relevant cellular pathways, to investigate the functions and potential mechanisms of PPP1R14B in the pathogenesis or clinical prognosis of different cancers. Herein, we found that PPP1R14B was involved in the prognosis of pan-cancer and closely related to immune infiltration. Increased PPP1R14B expression correlated with poor prognosis and increased immune infiltration levels in myeloid-derived suppressor cells (MDSCs). Our studies suggest that PPP1R14B can be used as a prognostic biomarker for pan-cancer. Our findings may provide an antitumor strategy targeting PPP1R14B, including manipulation of tumor cell growth or the tumor microenvironment, especially myeloid-derived suppressor cell infiltration.

scholarly journals TCGA Pan-Cancer Genomic Analysis of Alternative Lengthening of Telomeres (ALT) Related Genes

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 834
Author(s):  
Isaac Armendáriz-Castillo ◽  
Andrés López-Cortés ◽  
Jennyfer García-Cárdenas ◽  
Patricia Guevara-Ramírez ◽  
Paola E. Leone ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Genomic Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Telomere Maintenance ◽  
The Cancer Genome Atlas ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening ◽  
Pan Cancer

Telomere maintenance mechanisms (TMM) are used by cancer cells to avoid apoptosis, 85–90% reactivate telomerase, while 10–15% use the alternative lengthening of telomeres (ALT). Due to anti-telomerase-based treatments, some tumors switch from a telomerase-dependent mechanism to ALT; in fact, the co-existence between both mechanisms has been observed in some cancers. Although different elements in the ALT pathway are uncovered, some molecular mechanisms are still poorly understood. Therefore, with the aim to identify potential molecular markers for the study of ALT, we combined in silico approaches in a 411 telomere maintenance gene set. As a consequence, we conducted a genomic analysis of these genes in 31 Pan-Cancer Atlas studies from The Cancer Genome Atlas and found 325,936 genomic alterations; from which, we identified 20 genes highly mutated in the cancer studies. Finally, we made a protein-protein interaction network and enrichment analysis to observe the main pathways of these genes and discuss their role in ALT-related processes, like homologous recombination and homology directed repair. Overall, due to the lack of understanding of the molecular mechanisms of ALT cancers, we proposed a group of genes, which after ex vivo validations, could represent new potential therapeutic markers in the study of ALT.

scholarly journals Potential therapeutic targets in the tumor microenvironment of hepatocellular carcinoma: reversing the protumor effect of tumor-associated macrophages

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jingyi Zhou ◽  
Weiyu Wang ◽  
Qi Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Therapeutic Targets ◽  
Interaction Network ◽  
Cell Interaction ◽  
Macrophage Phenotype ◽  
Tumor Associated Macrophages ◽  
Dynamic Interactions ◽  
Immune Modulators

AbstractIn hepatocellular carcinoma patients, due to the microenvironmental specificity of liver, the tumor microenvironment exhibits high immunosuppression and drug resistance, resulting in excessive or insufficient responses to immunotherapy. The dynamic interactions between tumor cells and immune modulators in the TME significantly impact the occurrence and development of tumors, efficacy, and drug resistance, which can create a much more positive response to immunotherapy. Moreover, with the wide application of single-cell sequencing technology in the TME, increasing evidence shows an interaction network among cells. Sequencing results suggest that specific tumor-associated macrophages are a hub node, connecting different cell populations in the cell interaction network, and can could regulate tumor generation and antitumor immunity. This review focused on therapeutic targets that could be targeted to remodel the tumor microenvironment and reprogram the tumor-associated macrophage phenotype in hepatocellular carcinoma patients, thereby improving immunotherapeutic efficacy.

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