Prognostic Value and Immune Infiltration of HPV Related Genes in the Immune Microenvironment of Cervical Cancer

2021 ◽  
Author(s):  
Rui Chen ◽  
Luning Mao ◽  
Rui Shi ◽  
Linlin Chang ◽  
Guozeng Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Prognostic Value ◽  
Immune Microenvironment ◽  
Immune Infiltration

scholarly journals Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yunfeng Xu ◽  
Ze Zhang ◽  
Da Xu ◽  
Xin Yang ◽  
Lina Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Panel ◽  
Metabolic Reprogramming ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Immune Infiltration

Abstract Background Cumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment. Methods We compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n  =  28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n  =  60) and TCGA (n  =  411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan–Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY. Results We identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC.ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application. Conclusions We investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

scholarly journals Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

2021 ◽  
Author(s):  
Yunfeng Xu ◽  
Ze Zhang ◽  
Da Xu ◽  
Li-Na Zhou ◽  
Ying Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Panel ◽  
Metabolic Reprogramming ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Immune Infiltration

Abstract BackgroundCumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment.MethodsWe compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n = 28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n = 60) and TCGA (n = 411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms (TIMER, CIBERSORT, quanTIseq, xCell, MCP-counter, EPIC) and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan-Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY.ResultsWe identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC. According to the survival outcome and correlation analysis, ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application.ConclusionsWe investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

scholarly journals Comprehensive Analysis of Prognostic Significance and Immune Infiltration for FAM83 Family in Cervical Cancer

2021 ◽  
Author(s):  
Yue Qi ◽  
Yue Wang
Keyword(s):  
Cervical Cancer ◽  
Targeted Therapy ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Family Members ◽  
High Expression ◽  
Biological Behavior ◽  
Peptidase Activity ◽  
Immune Infiltration ◽  
Tumor Stages

Abstract Background: This study aimed to explore the expression of Family with sequence similarity 83 (FAM83) members in cervical cancer, its prognostic value, related signaling pathways, regulatory mechanisms, and immune infiltration. It’s of great value to explore the potential role of FAM83 family in cervical cancer and provide a new scientific basis for targeted therapy.Methods: The expression, gene mutations and prognostic value of FAM83 family members in cervical cancer were analyzed by various bioinformatics tools and databases. We further explored the interaction regulation network and immune infiltration between FAM83 family members and their closely related genes through a series of databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted.Results: This study showed that the expression levels of FAM83A/B/C/D/E/F/G/H gene were upregulated in cervical cancer, the expression of FAM83B/C/D/E/F/G/H were related to tumor stages of cervical cancer, and the promoter methylation of FAM83A/D/E/F/G genes in cervical cancer were lower than those in normal tissues. What’s more, high expression of FAM83A, FAM83B, and FAM83H mRNA was associated with shortened overall survival. GO results showed that FAM83A, FAM83B, and FAM83H and their closely related genes can play an important role in cell-cell junction, calcium-dependent protein binding, regulation of peptidase activity, inflammatory response. KEGG analysis results showed that FAM83A, FAM83B, and FAM83H and their closely related genes were significantly enriched in cancer pathways, estrogen signaling pathway, MAPK signaling pathway. Furthermore, FAM83A, FAM83B, and FAM83H are all closely related to lymphocytes (Tcm_CD4, Tcm_CD8, and neutrophils) and immunomodulators (TGFBR1, TGFB1, and TNFSF9).Conclusions: With multiple databases, we found that the high expression of FAM83A, FAM83B, and FAM83H were associated with the shortened survival time and poor prognosis in patients with cervical cancer, and also closely correlated with lymphocytes and immune infiltration, suggesting that FAM83A, FAM83B, and FAM83H played an important role in the occurrence, development, malignant biological behavior, and immune infilatration of cervical cancer, which provides an important theoretical basis for early diagnosis and targeted therapy for cervical cancer.

scholarly journals Comprehensive analysis of prognostic value and immune infiltration of kindlin family members in non-small cell lung cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoshan Su ◽  
Ning Liu ◽  
Weijing Wu ◽  
Zhixing Zhu ◽  
Yuan Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Immune Infiltration

Abstract Background Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated. Methods We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR. Results The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC. Conclusions The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.

Exploration of Tumor Mutation Burden Combined with Immune Infiltrates in the Prognosis of Lung Adenocarcinoma

2021 ◽  
Author(s):  
Zhenyu Zhao ◽  
Boxue He ◽  
Qidong Cai ◽  
Pengfei Zhang ◽  
Xiong Peng ◽  
...  
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Clinical Application ◽  
Risk Group ◽  
High Risk Group ◽  
Immune Microenvironment ◽  
Tumor Mutation Burden ◽  
Immune Signature ◽  
Immune Infiltration ◽  
Mutation Burden

Abstract Background: Lung adenocarcinoma (LUAD) accounts for a majority of cancer-related deaths worldwide annually. A recent study shows that immunotherapy is an effective method of LUAD treatment, and tumor mutation burden (TMB) was associated with the immune microenvironment and affected the immunotherapy. Exploration of the gene signature associated with tumor mutation burden and immune infiltrates in predicting prognosis in lung adenocarcinoma in this study, we explored the correlation of TMB with immune infiltration and prognosis in LUAD.Materials and Methods: In this study, we firstly got mutation data and LUAD RNA-Seq data of the LUAD from The Cancer Genome Atlas (TCGA), and according to the TMB we divided the patients into high/low-TMB levels groups. The gene ontology (GO) pathway enrichment analysis and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to explore the molecular function of the differentially expressed genes (DEGs) between the two groups. The function enrichment analyses of DEGs were related to the immune pathways. Then, the ESTIMATE algorithm, CIBERSORT, and ssGSEA analysis were utilized to identify the relationship between TMB subgroups and immune infiltration. According to the results, Venn analysis was utilized to select the immune-related genes in DEGs. Univariate and Lasso Cox proportional hazards regression analyses were performed to construct the signature which positively associated with the immune infiltration and affected the survival. Finally, we verified the correlation between the signature and immune infiltration. Result: The exploration of the immune infiltration suggested that high-TMB subgroups positively associated with the high level of immune infiltration in LUAD patients. According to the TMB-related immune signature, the patients were divided into High/Low-risk groups, and the high-risk group was positively associated with poor prognostic. The results of the PCA analysis confirmed the validity of the signature. We also verified the effectiveness of the signature in GSE30219 and GSE72094 datasets. The ROC curves and C-index suggested the good clinical application of the TMB-related immune signature in LUAD prognosis. Another result suggested that the patients of the high-risk group were positively associated with higher TMB levels, PD-L1expression, and immune infiltration levels.Conclusion: In conclusion, our signature provides potential biomarkers for studying aspects of the TMB in LUAD such as TMB affected immune microenvironment and prognosis. This signature may provide some biomarkers which could improve the biomarkers of PD-L1 immunotherapy response and were inverted for the clinical application of the TMB in LUAD. LUAD male patients with higher TMB-levels and risk scores may benefit from immunotherapy. The high-risk patients along with higher PD-L1 expression of the signature may suitable for immunotherapy and improve their survival by detecting the TMB of LUAD.

scholarly journals Cervical cancer prognosis and diagnosis using electrical impedance spectroscopy

2021 ◽  
Vol 12 (1) ◽  
pp. 153-162
Author(s):  
Ping Li ◽  
Peter E. Highfield ◽  
Zi-Qiang Lang ◽  
Darren Kell
Keyword(s):  
Cervical Cancer ◽  
Data Analysis ◽  
Impedance Spectroscopy ◽  
Cancer Diagnosis ◽  
Prognostic Value ◽  
Electrical Impedance ◽  
Electrical Impedance Spectroscopy ◽  
Physical Models ◽  
Tissue Structure ◽  
Classification Models

Abstract Electrical impedance spectroscopy (EIS) has been used as an adjunct to colposcopy for cervical cancer diagnosis for many years, Currently, the template match method is employed for EIS measurements analysis, where the measured EIS spectra are compared with the templates generated from three-dimensional finite element (FE) models of cancerous and non-cancerous cervical tissue, and the matches between the measured EIS spectra and the templates are then used to derive a score that indicates the association strength of the measured EIS to the High-Grade Cervical Intraepithelial Neoplasia (HG CIN). These FE models can be viewed as the computational versions of the associated physical tissue models. In this paper, the problem is revisited with an objective to develop a new method for EIS data analysis that might reveal the relationship between the change in the tissue structure due to disease and the change in the measured spectrum. This could provide us with important information to understand the histopathological mechanism that underpins the EIS-based HG CIN diagnostic decision making and the prognostic value of EIS for cervical cancer diagnosis. A further objective is to develop an alternative EIS data processing method for HG CIN detection that does not rely on physical models of tissues so as to facilitate extending the EIS technique to new medical diagnostic applications where the template spectra are not available. An EIS data-driven method was developed in this paper to achieve the above objectives, where the EIS data analysis for cervical cancer diagnosis and prognosis were formulated as the classification problems and a Cole model-based spectrum curve fitting approach was proposed to extract features from EIS readings for classification. Machine learning techniques were then used to build classification models with the selected features for cervical cancer diagnosis and evaluation of the prognostic value of the measured EIS. The interpretable classification models were developed with real EIS data sets, which enable us to associate the changes in the observed EIS and the risk of being HG CIN or developing HG CIN with the changes in tissue structure due to disease. The developed classification models were used for HG CIN detection and evaluation of the prognostic value of EIS and the results demonstrated the effectiveness of the developed method. The method developed is of long-term benefit for EIS–based cervical cancer diagnosis and, in conjunction with standard colposcopy, there is the potential for the developed method to provide a more effective and efficient patient management strategy for clinic practice.

scholarly journals Identification of Biomarkers Related to Immune Cell Infiltration in Hepatocellular Carcinoma Using Gene Co-Expression Network

2021 ◽  
Vol 27 ◽  
Author(s):  
Wanbang Zhou ◽  
Yiyang Chen ◽  
Ruixing Luo ◽  
Zifan Li ◽  
Guanwei Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Network Analysis ◽  
Tumor Progression ◽  
Protein Interactions ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Microenvironment ◽  
Hub Genes ◽  
Expression Levels ◽  
Immune Infiltration

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Due to the lack of effective biomarkers and its complex immune microenvironment, the effects of current HCC therapies are not ideal. In this study, we used the GSE57957 microarray data from Gene Expression Omnibus database to construct a co-expression network. The weighted gene co-expression network analysis and CIBERSORT algorithm, which quantifies cellular composition of immune cells, were used to identify modules related to immune cells. Four hub genes (EFTUD2, GAPDH, NOP56, PA2G4) were identified by co-expression network and protein-protein interactions network analysis. We examined these genes in TCGA database, and found that the four hub genes were highly expressed in tumor tissues in multiple HCC groups, and the expression levels were significantly correlated with patient survival time, pathological stage and tumor progression. On the other hand, methylation analysis showed that the up-regulation of EFTUD2, GAPDH, NOP56 might be due to the hypomethylation status of their promoters. Next, we investigated the correlations between the expression levels of four hub genes and tumor immune infiltration using Tumor Immune Estimation Resource (TIMER). Gene set variation analysis suggested that the four hub genes were associated with numerous pathways that affect tumor progression or immune microenvironment. Overall, our results showed that the four hub genes were closely related to tumor prognosis, and may serve as targets for treatment and diagnosis of HCC. In addition, the associations between these genes and immune infiltration enhanced our understanding of tumor immune environment and provided new directions for the development of drugs and the monitoring of tumor immune status.

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