scholarly journals Integrated Analysis of Angiogenesis-Mediated Tumor Immune Microenvironment Pattern in Hepatocellular Carcinoma (HCC) and a Novel Prognostic Model Construction to Predict Patient Outcome

2021 ◽  
Vol 27 ◽  
Author(s):  
Chengqian Lv ◽  
Qianqian Huang ◽  
Xu Zhang ◽  
Huimin Cai ◽  
Xuechun Ji ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Hepatocellular Carcinoma ◽  
Prognostic Model ◽  
Model Construction ◽  
Integrated Analysis ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

scholarly journals Integrated analysis of methylation-driven genes and pretreatment prognostic factors in patients with hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongsheng He ◽  
Shengyin Liao ◽  
Lifang Cai ◽  
Weiming Huang ◽  
Xuehua Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Risk Score ◽  
Prognostic Model ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
Calibration Plot ◽  
Clinical Parameters ◽  
T Stage

Abstract Background The potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy. This study aimed to integrate methylation-driven genes and pretreatment prognostic factors and then construct a new individual prognostic model in hepatocellular carcinoma (HCC) patients. Methods The gene methylation, gene expression dataset and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Methylation-driven genes were screened with a Pearson’s correlation coefficient less than − 0.3 and a P value less than 0.05. Univariable and multivariable Cox regression analyses were performed to construct a risk score model and identify independent prognostic factors from the clinical parameters of HCC patients. The least absolute shrinkage and selection operator (LASSO) technique was used to construct a nomogram that might act to predict an individual’s OS, and then C-index, ROC curve and calibration plot were used to test the practicability. The correlation between clinical parameters and core methylation-driven genes of HCC patients was explored with Student’s t-test. Results In this study, 44 methylation-driven genes were discovered, and three prognostic signatures (LCAT, RPS6KA6, and C5orf58) were screened to construct a prognostic risk model of HCC patients. Five clinical factors, including T stage, risk score, cancer status, surgical method and new tumor events, were identified from 13 clinical parameters as pretreatment-independent prognostic factors. To avoid overfitting, LASSO analysis was used to construct a nomogram that could be used to calculate the OS in HCC patients. The C-index was superior to that from previous studies (0.75 vs 0.717, 0.676). Furthermore, LCAT was found to be correlated with T stage and new tumor events, and RPS6KA6 was found to be correlated with T stage. Conclusion We identified novel therapeutic targets and constructed an individual prognostic model that can be used to guide personalized treatment in HCC patients.

scholarly journals Integrated Analysis of Methylation-driven Genes and Pretreatment Prognostic Factors in Patients with Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Dongsheng He ◽  
Lifang Cai ◽  
Weiming Huang ◽  
Xuehua Xie ◽  
Mengxing You ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Risk Score ◽  
Prognostic Model ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
Calibration Plot ◽  
Clinical Parameters ◽  
T Stage

Abstract Background: The potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy. This study aimed to integrate methylation-driven genes and pretreatment prognostic factors and then construct a new individual prognostic model in hepatocellular carcinoma (HCC) patients.Methods: The gene methylation, gene expression dataset and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Methylation-driven genes were screened with a Pearson’s correlation coefficient less than -0.3 and a P value less than 0.05. Univariable and multivariable Cox regression analyses were performed to construct a risk score model and identify independent prognostic factors from the clinical parameters of HCC patients. The least absolute shrinkage and selection operator (LASSO) technique was used to construct a nomogram that might act to predict an individual’s OS, and then C-index, ROC curve and calibration plot were used to test the practicability. The correlation between clinical parameters and core methylation-driven genes of HCC patients was explored with Student’s t-test.Results: In this study, 44 methylation-driven genes were discovered, and three prognostic signatures (LCAT, RPS6KA6, and C5orf58) were screened to construct a prognostic risk model of HCC patients. Five clinical factors, including T stage, risk score, cancer status, surgical method and new tumor events, were identified from 13 clinical parameters as pretreatment-independent prognostic factors. To avoid overfitting, LASSO analysis was used to construct a nomogram that could be used to calculate the OS in HCC patients. The C-index was superior to that from previous studies (0.75 vs 0.717, 0.676). Furthermore, LCAT was found to be correlated with T stage and new tumor events, and RPS6KA6 was found to be correlated with T stage.Conclusion: We identified novel therapeutic targets and constructed an individual prognostic model that can be used to guide personalized treatment in HCC patients.

scholarly journals pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma

2018 ◽  
Vol 7 (7) ◽  
pp. e1445452 ◽  
Author(s):  
Olga Kuchuk ◽  
Alessandra Tuccitto ◽  
Davide Citterio ◽  
Veronica Huber ◽  
Chiara Camisaschi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Human Hepatocellular Carcinoma ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

scholarly journals From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Yaojie Fu ◽  
Shanshan Liu ◽  
Shan Zeng ◽  
Hong Shen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Cell Lung ◽  
Immune Microenvironment ◽  
Liver Malignancy ◽  
The Third ◽  
Clinical Investigations ◽  
Tumor Immune Microenvironment ◽  
Novel Strategy ◽  
Immunosuppressive Microenvironment ◽  
Related Mortality

Abstract Hepatocellular carcinoma (HCC) ranks the most common primary liver malignancy and the third leading cause of tumor-related mortality worldwide. Unfortunately, despite advances in HCC treatment, less than 40% of HCC patients are eligible for potentially curative therapies. Recently, cancer immunotherapy has emerged as one of the most promising approaches for cancer treatment. It has been proven therapeutically effective in many types of solid tumors, such as non-small cell lung cancer and melanoma. As an inflammation-associated tumor, it’s well-evidenced that the immunosuppressive microenvironment of HCC can promote immune tolerance and evasion by various mechanisms. Triggering more vigorous HCC-specific immune response represents a novel strategy for its management. Pre-clinical and clinical investigations have revealed that various immunotherapies might extend current options for needed HCC treatment. In this review, we provide the recent progress on HCC immunology from both basic and clinical perspectives, and discuss potential advances and challenges of immunotherapy in HCC.

scholarly journals Prognostic Modeling of Patients with Metastatic Melanoma Based on Tumor Immune Microenvironment Characteristics

2021 ◽  
Author(s):  
Jing Liu ◽  
Ting Ye ◽  
Xue fang Zhang ◽  
Yong jian Dong ◽  
Wen feng Zhang ◽  
...  
Keyword(s):  
High Risk ◽  
Metastatic Melanoma ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
Risk Scores ◽  
Immune Microenvironment ◽  
Immune Infiltration ◽  
Tumor Immune Microenvironment

Abstract Most of the malignant melanomas are already in the middle and advanced stages when they are diagnosed, which is often accompanied by the metastasis and spread of other organs.Besides, the prognosis of patients is bleak. The characteristics of the local immune microenvironment in metastatic melanoma have important implications for both tumor progression and tumor treatment. In this study, data on patients with metastatic melanoma from the TCGA and GEO datasets were selected for immune, stromal, and estimate scores, and overlapping differentially expressed genes (DEGs) were screened. A nine-IRGs prognostic model (ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) was established by univariate COX regression, LASSO and multivariate COX regression. Receiver operating characteristic (ROC) curves were used to test the predictive accuracy of the model. Immune infiltration was analyzed by using CIBERSORT, Xcell and ssGSEA in high-risk and low-risk groups. The immune infiltration of the high-risk group was significantly lower than that of the low-risk group. Immune checkpoint analysis revealed that the expression of PDCD1, CTLA4, TIGIT, CD274, HAVR2 and LAG3 were significantly different in groups with different levels of risk scores. WGCNA analysis found that the yellow-green module contained seven genes (ALOX5AP, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) from the nine-IRG prognostic model, of which the yellow-green module had the highest correlation with risk scores. The results of GO and KEGG suggested that the genes in the yellow-green module were mainly enriched in immune-related biological processes. Finally, we analyzed the prognostic ability and expression characteristics of ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22 in metastatic melanoma. Overall, a prognostic model for metastatic melanoma based on the characteristics of the tumor immune microenvironment was established, which was helpful for further studies.It could function well in helping people to understand the characteristics of the immune microenvironment in metastatic melanoma and to find possible therapeutic targets.

scholarly journals Systematic pan-cancer landscape identifies CARM1 as a potential prognostic and immunological biomarker

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yingqi Qiu ◽  
Hao Wang ◽  
Peiyun Liao ◽  
Binyan Xu ◽  
Rong Hu ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Integrated Analysis ◽  
Regulation Of Transcription ◽  
Immune Microenvironment ◽  
Arginine Methyltransferase ◽  
Clinical Prognosis ◽  
Tumor Immune Microenvironment ◽  
Arginine Residues ◽  
Pan Cancer

Abstract Background Belonging to the protein arginine methyltransferase (PRMT) family, the enzyme encoded by coactivator associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of protein arginine residues, especially acts on histones and other chromatin related proteins, which is essential in regulating gene expression. Beyond its well-established involvement in the regulation of transcription, recent studies have revealed a novel role of CARM1 in tumorigenesis and development, but there is still a lack of systematic understanding of CARM1 in human cancers. An integrated analysis of CARM1 in pan-cancer may contribute to further explore its prognostic value and potential immunological function in tumor therapy. Results Based on systematic analysis of data in multiple databases, we firstly verified that CARM1 is highly expressed in most tumors compared with corresponding normal tissues, and is bound up with poor prognosis in some tumors. Subsequently, relevance between CARM1 expression level and tumor immune microenvironment is analyzed from the perspectives of tumor mutation burden, microsatellite instability, mismatch repair genes, methyltransferases genes, immune checkpoint genes and immune cells infiltration, indicating a potential relationship between CARM1 expression and tumor microenvironment. A gene enrichment analysis followed shortly, which implied that the role of CARM1 in tumor pathogenesis may be related to transcriptional imbalance and viral carcinogenesis. Conclusions Our first comprehensive bioinformatics analysis provides a broad molecular perspective on the role of CARM1 in various tumors, highlights its value in clinical prognosis and potential association with tumor immune microenvironment, which may furnish an immune based antitumor strategy to provide a reference for more accurate and personalized immunotherapy in the future.

scholarly journals Wnt/β-catenin Inhibitor ICG-001 Enhances the Antitumor Efficacy of Radiotherapy by Increasing Radiation-induced DNA Damage and Improving Tumor Immune Microenvironment in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Yan Huang ◽  
Hailong Sheng ◽  
Yazhi Xiao ◽  
Zhihong Zhang ◽  
Yiyao Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Critical Role ◽  
Tumor Control ◽  
Immune Microenvironment ◽  
Tumor Bearing ◽  
Pathway Activation ◽  
Tumor Immune Microenvironment ◽  
Radiotherapy Alone

Abstract Background: Radiotherapy has a promising anti-tumor effect in hepatocellular carcinoma (HCC), depending on the its regulatory effects on both cancer cells and tumor immune microenvironment (TME). Wnt/β-catenin signaling pathway activation, which is one of the most common alterations in HCC patients, has been reported to induce radioresistance, and also create immunosuppressive TME. However, it is unclear whether inhibition of wnt/β-catenin pathway could enhance the treatment efficacy of radiotherapy. In this study, we aim to explore the effect of wnt/β-catenin inhibitor ICG-001 in combination with radiotherapy and the underlying mechanism in HCC.Methods: C57BL/6 and nude mouse subcutaneous tumor models were used to evaluate the efficacy of different treatment regimens in tumor growth control, tumor recurrence inhibition and survival improvement. Flow cytometry was performed to assess the alterations of tumor infiltrating lymphocytes (TILs). Radioresistance was investigated by clone formation assay and γ-H2AX measurements. Wnt/β-catenin and cGAS/STING pathway activation was detected by immunoblotting. Results: The addition of ICG-001 to radiotherapy exhibited better anti-tumor control efficacy in tumor-bearing C57BL/6 mice than nude mice, which suggested that ICG-001 had a critical role in activating TME. The comprehensive analysis of TILs revealed that compared with radiotherapy alone, the combination of ICG-001 with radiotherapy boosted the infiltration and IFN-γ production ability of TIL CD8+ T cells, meanwhile reduced the number of TIL Tregs. Moreover, mechanism study demonstrated that ICG-001 exerted a radiosensitizing effect on HCC cells, thus leading to stronger activation of cGAS/STING signaling pathway upon radiotherapy in vitro and in vivo. Utilization of STING inhibitor, C-176, significantly impaired the synergetic effect of ICG-001 with radiotherapy on tumor control and TME activation. Furthermore, combination therapy led to a stronger immunologic memory and lasting anti-tumor immunity than radiotherapy, thus preventing tumor relapse in HCC tumor-bearing mice.Conclusion: Our findings showed that ICG-001 increased radioresistance and improved TME upon radiotherapy in HCC. Compared with radiotherapy alone, the combination of ICG-001 with radiotherapy displayed better therapeutic efficacy in inhibiting tumor growth, prolonging survival, and preventing recurrence in tumor-bearing mice. These data indicated that ICG-001 might be a potential synergetic treatment for radiotherapy and radioimmunotherapy in HCC.

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