scholarly journals A novel panel based on Immune infiltration and tumor mutational burden for prognostic prediction in hepatocellular carcinoma

2020 ◽  
Author(s):  
Hewei Wu ◽  
Xingrong Zheng ◽  
Tao Pan ◽  
Xiaoan Yang ◽  
Genglin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell Activation ◽  
Cell Activation ◽  
Gene Mutations ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Matrix Composition ◽  
Immune Infiltration ◽  
Tumor Mutational Burden ◽  
Worse Prognosis

Abstract Background : Tumor mutation burden (TMB) was associated with prognosis in various malignancies, but it remains to be elucidated in hepatocellular carcinoma (HCC). We aimed to investigate the prognostic effects of TMB and its relationship with immune infiltration so as to establish a panel model capable of predicting prognosis. Methods : TMB was calculated in all 374 HCC patients from the Cancer Genome Atlas, and high TMB and low TMB groups were determined based on propensity score matching and X-tile analysis. WCGNA was utilized to screen out genes related to immune cells and TMB, followed by multivariate analysis to generated the final TMB-Infiltration (TMB-IF) panel. 453 HCC patients from ICGC-LIRI-JP, GSE76427 and GSE20017 verified the robustness and extensibility of TMB-IF. Additionally, whole-exome sequencing (WES) was performed in 8 follow-up patients to investigate the relationship between HCC recurrence and TMB. Results : Patients in high TMB group had worse prognosis than those in low TMB group, with a cutoff TMB value of 4.9. Enrichment analysis demonstrated that differentially expressed genes were mainly related to T cell activation, cell membrane localization and matrix composition. Tumor immune infiltration analysis revealed the infiltrations of Th2, Th17, and Tgd were up-regulated in high TMB group, while those of Tr1, MAIT, and DC were up-regulated in low TMB group. And TMB-IF fit well with the actual survival observation, with a C-index 0.785 (0.700-0.870), which verified in ICGC-LIRI-JP was 0.670 (0.573-0.767), and 0.774 (0.670-0.877) in GSE76427. In addition, TMB-IF showed a good performance in predicting tumor vascular invasion with a C-index of 0.847 (0.778-0.916). Conclusions : Higher TMB means worse prognosis in HCC patients. Patients with higher frequency of immune-related gene mutations and TMB are prone to relapse after radical treatment.

scholarly journals Up-regulated Expression and Related Gene Regulatory Networks of ANLN Predict Poor Prognosis and Correlate with Immune Infiltration in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Bo Hu ◽  
Xiao-Bo Yang ◽  
Xinting Sang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Regulatory Networks ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Immune Infiltration ◽  
Dismal Prognosis ◽  
Mrna Binding

Abstract Background: The aberrant Anillin (ANLN) expression is reported to be associated with carcinogenesis. In this study, sequencing data collected from the Cancer Genome Atlas database were utilized to analyze ANLN expression in hepatocellular carcinoma (HCC).Methods: The relationships of clinicopathological features with ANLN were investigated, and gene set enrichment analysis (GSEA) was performed to reveal the ANLN-related functions. LinkedOmics was employed to identify the co-expressed genes of ANLN and to examine the target networks of kinases, microRNAs (miRNAs) and transcription factors (TFs). Besides, the correlation of ANLN expression with cancer immune infiltrates was analyzed by TIMER. Results: ANLN over-expression predicted dismal prognosis, and GESA results revealed several functions that were related to cell cycle and mRNA binding. Moreover, functional network analysis indicated that, ANLN might regulate DNA replication and cell cycle signaling through pathways that involved several cancer-related kinases, miRNAs and E2F1. Additionally, ANLN was suggested to be associated with the infiltration of several immune cells, which was proved to be upregulated in both HCC cells and tissues. Conclusion: Those efficiently mined data reveal information regarding ANLN expression, the potential regulatory networks and the relationship with immune infiltration in HCC, which lay a foundation for further study on the role of ANLN in carcinogenesis.

scholarly journals A Pyroptosis-Related LncRNA Signature for Predicting Prognosis and Treatment in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yuhao Zhang ◽  
Jiaxin Zhang ◽  
Fengxian Wei ◽  
Haodong Zhang ◽  
Dongdong Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Immune Cell ◽  
Cox Regression ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Clinical Treatment ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Infiltration

Abstract Background: Hepatocellular carcinoma (HCC), which carries a very bad prognosis, is a common malignant tumor worldwide. This study aim to identify a pyroptosis-related long non-coding RNA(pyLncRNA) prognostic signature in HCC by integrated bioinformatics analysis. Methods: All expression profiles of HCC were obtained from The Cancer Genome Atlas (TCGA) and pyroptosis-related genes were from the GSEA website. After identified differentially expressed pyLncRNAs, univariate Cox regression and Lasso analysis were used to identify a pyroptosis-related LncRNAs prognositic signature(py-LPS). Internal validation was used to validate the prognostic value of the py-LPS via the Kaplan-Meier(K-M) curve and receiver operating characteristic(ROC) curve. Additional, we established the nomogram and analyzed the correlation between the signature and immune immune infiltration as well as clinical treatment. Result: 7 pyLncRNAs were established the signature for HCC prognosis. K-M curves exhibited the low risk group presented a markedly longer OS than the high. Clinical subgroups analysis based age, gender, grade and stage yielded the similar results. The signature had an independent prognostic value for HCC(p<0.001). Nomogram estimated one-, three- and five-year survival were 0.777, 0.741 and 0.709. Then, gene set enrichment analysis(GSEA) demostrated significant pathways. Futhermore, we found immune cell infiltration and immunotherapy targets was associated with the signature,which could provided clinical recommendations for chemotherapy.Conclusion: In this study, a novel pyroptosis-related LncRNAs porgnostic signature of HCC, correlated with immune infiltration, could predict the survival of HCC patients and give suggestions for clinical treatment.

scholarly journals Identification of LOXL3-Associating Immune Infiltration Landscape and Prognostic Value in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Ning Wang ◽  
Xue Zhou ◽  
Fei Tang ◽  
Xue Wang ◽  
Xiaowei Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell Activation ◽  
Immune Checkpoint ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Lysyl Oxidase ◽  
Enrichment Analysis ◽  
Tumor Immunotherapy ◽  
Functional Enrichment ◽  
Elastic Fibers

Abstract Hepatocellular carcinoma (HCC), the most common type of hepatic malignancies, remains a global health challenge with multiple aetiologies and low five-year survival rate. In recent years, breakthroughs in the field of tumor immunotherapy with immune checkpoint inhibitors (ICIs) have made a therapeutic revolution, which has been shown to improve the prognosis of patients with HCC. Immune infiltrates represent a major component of tumor microenvironment (TME), and play an essential role in both tumor progression and therapeutic response. The major unmet challenge in tumor immunotherapy is exploring the intrinsic and extrinsic mechanisms of TME promoting the management of HCC. Lysyl oxidase like 3 (LOXL3) participates in the remodeling of extracellular matrix (ECM) and the cross-linking of collagen and elastic fibers. It has been reported that LOXL3 is associated with the development and tumorigenesis of multiple types of cancer. In this study, we first found that LOXL3 gene was upregulated in tumor tissues compared with the normal tissues. Furthermore, LOXL3 expression is positively correlated with the infiltration of multiple immune cells and the expression of immune checkpoint genes in HCC. Meanwhile, high LOXL3 expression predicted poor outcomes of the patients with HCC. Functional enrichment analysis suggested that LOXL3 was mainly linked to extracellular structure and matrix organization, cell−cell adhesion, and T cell activation. This is the first comprehensive study to indicate that LOXL3 is correlated with immune infiltrates and may serve as a novel biomarker predicting prognosis and immunotherapy in HCC.

Identification of prognostic genes from the breast cancer microenvironment

2020 ◽  
Author(s):  
Xiao-lu Zhang ◽  
Jia Wang ◽  
Cun Liu ◽  
Chun-di Gao ◽  
Jing Zhuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Patients ◽  
Ppi Network

Abstract Background Prognostic evaluation of breast cancer is crucial in deciding the course of clinical treatment. The levels of immune cells and stromal cells in tumor microenvironment provide a new approach to evaluate the prognosis of breast cancer.Method: We obtained mRNA gene expression profiles of breast cancer patients from The Cancer Genome Atlas (TCGA), evaluated immune and stromal scores in tumor microenvironment (TME) using the ESTIMATE algorithm. We also constructed a protein-protein interaction (PPI) network, and performed function enrichment analysis and prognostic analysis.Results A total of 898 samples were divided into two groups corresponding to high and low score for both stromal as well as immune scores. 247 differentially expressed genes were identified, most of which were associated with T cell activation, lymphocyte differentiation, and cytokine receptor activity. We finally found 10 hub genes. Among them, we were able to confirm the following genes significantly association with prognosis: CCR5, CD2, CD3E, and CD5. Two important modules were isolated from the PPI network and for further analysis.Conclusion This study identified a group of genes significantly associated with the prognosis of breast cancer, and their efficacy still requires further clinical data validation.

scholarly journals An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Dengliang Lei ◽  
Yue Chen ◽  
Yang Zhou ◽  
Gangli Hu ◽  
Fang Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Roc Curves ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Highly Correlated

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA (lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of patients with liver cancer, but its mechanism of action must be further elucidated by experiments.

scholarly journals Identification of Potential Biomarkers and Related Transcription Factors in Peripheral Blood of Tuberculosis Patients

2020 ◽  
Vol 17 (19) ◽  
pp. 6993
Author(s):  
Longxiang Xie ◽  
Xiaoyu Chao ◽  
Tieshan Teng ◽  
Qiming Li ◽  
Jianping Xie
Keyword(s):  
Transcription Factors ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarkers

Tuberculosis (TB), one major threat to humans, can infect one third of the worldwide population, and cause more than one million deaths each year. This study aimed to identify the effective diagnosis and therapy biomarkers of TB. Hence, we analyzed two microarray datasets (GSE54992 and GSE62525) derived from the Gene Expression Omnibus (GEO) database to find the differentially expressed genes (DEGs) of peripheral blood mononuclear cell (PBMC) between TB patients and healthy specimens. Functional and pathway enrichment of the DEGs were analyzed by Metascape database. Protein-protein interaction (PPI) network among the DEGs were constructed by STRING databases and visualized in Cytoscape software. The related transcription factors regulatory network of the DEGs was also constructed. A total of 190 DEGs including 36 up-regulated genes and 154 down-regulated genes were obtained in TB samples. Gene functional enrichment analysis showed that these DEGs were enriched in T cell activation, chemotaxis, leukocyte activation involved in immune response, cytokine secretion, head development, etc. The top six hub genes (namely, LRRK2, FYN, GART, CCR7, CXCR5, and FASLG) and two significant modules were got from PPI network of DEGs. Vital transcriptional factors, such as FoxC1 and GATA2, were discovered with close interaction with these six hub DEGs. By systemic bioinformatic analysis, many DEGs associated with TB were screened, and these identified hub DEGs may be potential biomarkers for diagnosis and treatment of TB in the future.

scholarly journals Identification of the HMMR Gene as a Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma Based on Integrated Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Honglan Guo ◽  
Qinqiao Fan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Roc Curve ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Roc Curve Analysis ◽  
Cox Regression Analysis ◽  
Normal Tissues

Background. We aimed to investigate the expression of the hyaluronan-mediated motility receptor (HMMR) gene in hepatocellular carcinoma (HCC) and nonneoplastic tissues and to investigate the diagnostic and prognostic value of HMMR. Method. With the reuse of the publicly available The Cancer Genome Atlas (TCGA) data, 374 HCC patients and 50 nonneoplastic tissues were used to investigate the diagnostic and prognostic values of HMMR genes by receiver operating characteristic (ROC) curve analysis and survival analysis. All patients were divided into low- and high-expression groups based on the median value of HMMR expression level. Univariate and multivariate Cox regression analysis were used to identify prognostic factors. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism of the HMMR genes involved in HCC. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC). Results. HMMR mRNA expression was significantly elevated in HCC tissues compared with that in normal tissues from both TCGA and the ICGC cohorts (all P values <0.001). Increased HMMR expression was significantly associated with histologic grade, pathological stage, and survival status (all P values <0.05). The area under the ROC curve for HMMR expression in HCC and normal tissues was 0.969 (95% CI: 0.948–0.983) in the TCGA cohort and 0.956 (95% CI: 0.932–0.973) in the ICGC cohort. Patients with high HMMR expression had a poor prognosis than patients with low expression group in both cohorts (all P < 0.001 ). Univariate and multivariate analysis also showed that HMMR is an independent predictor factor associated with overall survival in both cohorts (all P values <0.001). GSEA showed that genes upregulated in the high-HMMR HCC subgroup were mainly significantly enriched in the cell cycle pathway, pathways in cancer, and P53 signaling pathway. Conclusion. HMMR is expressed at high levels in HCC. HMMR overexpression may be an unfavorable prognostic factor for HCC.

scholarly journals Significance of HMMR Overexpression in Hepatocellular Carcinoma

2022 ◽  
Author(s):  
Weidong Zhao ◽  
Zhengxiang Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Enrichment Analysis ◽  
Progression Free Survival ◽  
Expression Level ◽  
Marker Genes ◽  
Surface Binding ◽  
Free Survival ◽  
Immune Infiltration ◽  
The Relationship

Abstract Background: Hyaluronan Mediated Motility Receptor (HMMR), as one of the key surface binding proteins of HA, is up-regulated in many tumors. What’s more, the expression level of HMMR is usually correlate with tumor progression and prognosis. However, the relationship between the expression of HMMR and the prognosis and immune infiltration of hepatocellular carcinoma (HCC) is still unclear.Methods: We analyzed the expression level of HMMR by TIMER database, GEO database and GEPIA database. The correlation between the HMMR expression and tumor prognosis was analyzed via the Kaplan-Meier plots. The TIMER database and GEPIA database were used to study the relationship between HMMR expression and immune infiltration. GO and KEGG enrichment analysis were used to explore the potential biological functions of HMMR.Results: HMMR expression was significantly higher in several human cancers, including HCC, than in corresponding normal tissues. High HMMR expression associated with poorer overall survival, disease-specific survival, progression-free survival and relapse-free survival in HCC patients. HMMR showed strong correlation with tumor-infiltrating B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and dendritic cells. Several immune marker genes expression, including CD86, IRF5, CD11b, KIRIDL4, CD11c, IFN-γ, STAT3, STAT5B, and CTLA4, have markedly positive correlations with HMMR expression. Enrichment analysis found that HMMR is mainly involved in cell cycle, DNA replication and repair, PLK1 pathway, E2F pathway, ATR pathway and AURORA B pathway.Conclusions: HMMR is a potential prognostic biomarker that influence tumor progression and correlated with tumor immune cells infiltration in HCC.

scholarly journals CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Di Yang ◽  
Jian Ma ◽  
Xiao-Xin Ma
Keyword(s):  
Endometrial Cancer ◽  
Immune Cell ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Infiltration ◽  
Lncrna Expression ◽  
Ec Cells

The prognosis of patients with endometrial cancer (EC) is closely associated with immune cell infiltration. Although abnormal long non-coding RNA (lncRNA) expression is also linked to poor prognosis in patients with EC, the function and action mechanism of immune infiltration-related lncRNAs underlying the occurrence and development of EC remains unclear. In this study, we analyzed lncRNA expression using The Cancer Genome Atlas and clinical data and identified six lncRNAs as prognostic markers for EC, all of which are associated with the infiltration of immune cell subtypes, as illustrated by ImmLnc database and ssGSEA analysis. Real-time quantitative polymerase chain reaction showed that CDKN2B-AS1 was significantly overexpressed in EC, whereas its knockdown inhibited the proliferation and invasion of EC cells and the in vivo growth of transplanted tumors in nude mice. Finally, we constructed a competing endogenous RNA regulatory network and conducted Gene Ontology enrichment analysis to elucidate the potential molecular mechanism underlying CDKN2B-AS1 function. Overall, we identified molecular targets associated with immune infiltration and prognosis and provide new insights into the development of molecular therapies and treatment strategies against EC.

scholarly journals CXCL5 Has Potential to Be a Marker for Hepatocellular Carcinoma Prognosis and Was Correlating With Immune Infiltrates

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan Nie ◽  
Mei-chun Jiang ◽  
Cong Liu ◽  
Qi Liu ◽  
Xuan Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Hospital Data ◽  
Gene Set Enrichment ◽  
Local Hospital ◽  
High Expression Group ◽  
Cancer Genome Atlas

BackgroundsTumor microenvironment (TME) plays a crucial role in the initiation and progression of Hepatocellular Carcinoma (HCC), especially immune infiltrates. However, there is still a challenge in understanding the modulation of the immune and stromal components in TME, especially TME related genes.MethodsThe proportion of tumor-infiltrating immune cells (TICs) and the immune and stromal scores in 374 HCC patients from The Cancer Genome Atlas (TCGA) database were determined using CIBERSORT and ESTIMATE computational methods. The final screened genes were confirmed by the PPI network and univariate Cox regression of the differentially expressed genes based on different immune or stromal scores. The correlation between the expression levels of the final gene interactions and the clinical characteristics was based on TCGA database and local hospital data. Gene set enrichment analysis (GSEA) and the effect of CXCL5 expression on TICs were conducted.ResultsThere were correlations between the expression of CXCL5 and survival of HCC patients and TMN classification both in TCGA database and local hospital data. The immune-related activities were enriched in the high-expression group; however, the metabolic pathways were enriched in the low-expression group. The result of CIBERSORT analyzing had indicated that CXCL5 expression were correlated with the proportion of NK cells activated, macrophages M0, Mast cells resting, Neutrophils.ConclusionsCXCL5 was a potential prognostic marker for HCC and provides clues regarding immune infiltrates, which offers extra insight for therapeutics of HCC, however, more independent cohorts and functional experiments of CXCL5 are warranted.

Sign in / Sign up

Export Citation Format

Share Document