Dataset Information

Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma.

ABSTRACT: Most cancers have a downregulation of Fidgetin (FIGN), which has been linked to tumor growth. However, there aren't many papers that mention FIGN's connection to hepatocellular carcinoma (HCC). Here, FIGN expression in HCC tissues was markedly reduced as compared to nearby normal liver tissues. According to univariate and multivariate Cox regression, it served as an independent predictor of survival outcomes. Patients with high levels of FIGN expression had a worse outcome. FIGN was shown to be engaged in immune-related pathways and to have a positive correlation with immunological score and immune cells according to KEGG pathway analysis. In HCC patients, FIGN was substantially linked with immunological checkpoints and the hot tumor state. Additionally, immunotherapy and chemotherapy showed a significant therapeutic response in HCC patients with low FIGN expression. This research revealed that FIGN expression was tightly related to hepatoma immunity and might be employed as a biomarker to predict patient prognosis and guide medication.

SUBMITTER: Qi L

PROVIDER: S-EPMC10968695 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma.

Qi Longju L Chen Shiyuan S Liao Zehua Z Fan Mengjie M Zhang Jiayi J Gao Yuan Y Shen Jiabao J Sun Yuyu Y Wang Qinghua Q

Aging 20240227 5

Most cancers have a downregulation of Fidgetin (FIGN), which has been linked to tumor growth. However, there aren't many papers that mention FIGN's connection to hepatocellular carcinoma (HCC). Here, FIGN expression in HCC tissues was markedly reduced as compared to nearby normal liver tissues. According to univariate and multivariate Cox regression, it served as an independent predictor of survival outcomes. Patients with high levels of FIGN expression had a worse outcome. FIGN was shown to be ...[more]

PMID: 38421251

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Project description:BackgroundFerroptosis is a type of regulatory cell death (RCD) mode that depends on iron-mediated oxidative damage. It has the potential to improve the efficacy of tumor immunotherapy by modulating the tumor microenvironment (TME). Currently, immunotherapy has significantly improved the overall treatment strategy for advanced hepatocellular carcinoma (HCC), but the distinct immune microenvironment and high tolerance to the immune make massive differences in the immunotherapy effect of HCC patients. As a result, it is imperative to classify HCC patients who may benefit from immune checkpoint therapy. Simultaneously, the predictive value of ferroptosis in HCC and its potential role in TME immune cell infiltration also need to be further clarified.MethodsThree ferroptosis molecular models were built on the basis of mRNA expression profiles of ferroptosis-related genes (FRGs), with notable variations in immunocyte infiltration, biological function, and survival prediction. In order to further investigate the predictive impact of immunotherapy response in HCC patients, the ferroptosis score was constructed using the principal component analysis (PCA) algorithm to quantify the ferroptosis molecular models of individual tumors.ResultsIn HCC, there were three totally different ferroptosis molecular models. The ferroptosis score can be used to assess genetic variation, immunotherapy response, TME characteristics, and prognosis. Notably, tumors with low ferroptosis scores have extensive tumor mutations and immune exhaustion, which are associated with a poor prognosis and enhanced immunotherapy response.ConclusionsOur study indicates that ferroptosis plays an indispensable role in the regulation of the tumor immune microenvironment. For HCC, the ferroptosis score is an independent prognostic indicator. Assessing the molecular model of ferroptosis in individual tumors will assist us in better understanding the characteristics of TME, predicting the effect of immunotherapy in HCC patients, and thus guiding a more reasonable immunotherapy program.

Project description:Accumulating studies have highlighted the biologic significances of ferroptosis modification in tumor progression, but little is known whether ferroptosis modification patterns have potential roles in tumor microenvironment (TME) immune cell infiltration of hepatocellular carcinoma (HCC). In this study, we evaluated 51 ferroptosis regulators and performed consensus clustering algorithm to determine ferroptosis modification patterns and the ferroptosis related gene signature in HCC. Gene set variation analysis (GSVA) was employed to explore biological molecular variations in distinct ferroptosis modification patterns. Single sample gene set enrichment analysis (ssGSEA) algorithm was performed to quantify the relative infiltration levels of various immune cell subsets. Principal component analysis (PCA) algorithm was used to construct the ferroptosisSig score to quantify ferroptosis modification patterns of individual tumors with immune responses. Three distinct ferroptosis modification patterns were identified. GSVA enrichment analysis indicated that three ferroptosis modification subgroups were enriched in different metabolic pathways. ssGSEA analysis determined that 19 of 24 immune infiltrating cells had significant differences in three distinct ferroptosis patterns. A 91-ferroptosis gene signature was constructed to stratify patients into two ferroptosisSig score groups. Patients in the higher ferroptosisSig score were characterized by significantly prolonged survival time compared with patients in the lower ferroptosisSig score group (p < .0001). An immunotherapy cohort confirmed patients with higher ferroptosisSig score determined significant therapeutic advantages and clinical benefits. Receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of anti-PD/L1 immunotherapy by ferroptosisSig score. Our study indicated the ferroptosis modification played a significant role in TME heterogeneity and complexity. Evaluating the ferroptosis modification pattern of individual tumor could strengthen our cognition of TME infiltration characteristics and guide more effective clinic immunotherapy strategies.

Project description:Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the third leading cause of tumor-related mortality worldwide. In recent years, the emergency of immune checkpoint inhibitor (ICI) has revolutionized the management of HCC. Especially, the combination of atezolizumab (anti-PD1) and bevacizumab (anti-VEGF) has been approved by the FDA as the first-line treatment for advanced HCC. Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing to drug resistance and frequent recurrence. The tumor microenvironment (TME) of HCC is a complex and structured mixture characterized by abnormal angiogenesis, chronic inflammation, and dysregulated extracellular matrix (ECM) remodeling, collectively contributing to the immunosuppressive milieu that in turn prompts HCC proliferation, invasion, and metastasis. The tumor microenvironment coexists and interacts with various immune cells to maintain the development of HCC. It is widely accepted that a dysfunctional tumor-immune ecosystem can lead to the failure of immune surveillance. The immunosuppressive TME is an external cause for immune evasion in HCC consisting of 1) immunosuppressive cells; 2) co-inhibitory signals; 3) soluble cytokines and signaling cascades; 4) metabolically hostile tumor microenvironment; 5) the gut microbiota that affects the immune microenvironment. Importantly, the effectiveness of immunotherapy largely depends on the tumor immune microenvironment (TIME). Also, the gut microbiota and metabolism profoundly affect the immune microenvironment. Understanding how TME affects HCC development and progression will contribute to better preventing HCC-specific immune evasion and overcoming resistance to already developed therapies. In this review, we mainly introduce immune evasion of HCC underlying the role of immune microenvironment, describe the dynamic interaction of immune microenvironment with dysfunctional metabolism and the gut microbiome, and propose therapeutic strategies to manipulate the TME in favor of more effective immunotherapy.

Project description:AbstractGrowing evidence supports that the tumor microenvironment plays a key role in the development and progression of tumors. But immune microenvironment of hepatocellular carcinoma (HCC) has not yet been fully explored. In the present investigation, the clinical value and prognostic significance of immune-related genes in HCC were investigated.The immune and stromal scores of HCC were calculated through the application of Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Algorithm based on the Cancer Genome Atlas database. Differentially expressed genes were identified using the "edgeR" package of the R software. Functional annotation and pathway enrichment were performed using "ggplots2" and "clusterProfiler" packages in R software. Protein-protein interaction network was constructed using STRING, and the hub genes were identified through the Cytoscape. Survival analysis was performed using Kaplan-Meier methods. Tumor Immune Estimation Resource algorithm was used to view the immune landscape of the microenvironment in HCC.Firstly, the immune and stromal scores of HCC were calculated and we found that the immune and stromal scores of HCC were closely related to the patients' prognosis. Then the differentially expressed genes were identified respectively stratified by the median value of the immune and stromal scores, and the immune-related genes that related to the prognosis in HCC patients were further identified. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune-related biological process. In addition, dendritic cells were found to be the most abundant in the microenvironment of HCC through Tumor Immune Estimation Resource algorithm and were significantly associated with the patients' prognosis. To robust the results, the immune-related genes were validated in an independent dataset from the Gene Expression Omnibus database.We arrived at a more comprehensive understanding of the microenvironment of HCC and extracted 7 immune-related genes that were significantly associated with the recurrence survival of HCC.

Dataset Information

Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma.

Publications

Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma.

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