Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis

Yin, Lu; Zhou, Liuzhi; Xu, Ruochen

doi:10.21203/rs.3.rs-63032/v1

Cited by 10 publications

(8 citation statements)

References 15 publications

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“…At the same time, we also found that the most frequent type of non-nonsense mutation, whether in the low-or high-risk group, was a missense mutation. The top 3 genes with the highest frequency were TP53, TTN, and CTNNB1, respectively, which was consistent with previous studies (39,40). However, we found that the genes with the highest mutation frequency among high-and lowrisk groups differed, with CTNNB1 highest in the low-risk group and TP53 highest in the high-risk group.…”

Section: Discussionsupporting

confidence: 91%

Bioinformatics analysis of immune infiltrates and tripartite motif (TRIM) family genes in hepatocellular carcinoma

Cao¹,

Su²,

Peng³

et al. 2022

J Gastrointest Oncol

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Background: The tripartite motif (TRIM) family are important members of the Gene-finger-containing E3 ubiquitin-conjugating enzyme and are involved in the progression of hepatocellular carcinoma (HCC).Previous studies have largely focused on gene expression and molecular pathways, while the underlying role of the TRIM family in the tumor immune microenvironment (TIME) remains poorly understood. Methods:We systematically explored the correlations of prominent TRIM genes with immune checkpoints and immune infiltrates in 231 HCC samples [International Cancer Genome Consortium (ICGC) cohort (n=231); The Cancer Genome Atlas (TCGA) cohort (n=370)]. A prognostic risk model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis in the ICGC cohort. Kaplan-Meier curves based on the overall survival (OS) were used to assess differences in survival between clusters. We utilized gene set variation analysis (GSVA) to characterize the differences in biological functions. Based on univariate and multivariate Cox progression analysis, we developed a risk score signature and verified its reliability and validity. The Tumor Immune Single-cell Hub (TISCH) single-cell database was employed to evaluate the correlation of TRIM genes with the tumor microenvironment.Results: Cluster 1 was preferentially associated with a favorable prognosis (P<0.001). The amino acid, fatty acid, and drug metabolism pathways were significantly enriched in cluster 2. A prognosis risk score project was established and evaluated based on the 9 independent prognostic genes (all P<0.05). The immune score and stromal scores of patients with low-risk scores were greater than those of patients with high-risk scores (all P<0.001). However, patients with a high-risk score exhibited lower responses to immune checkpoint inhibitors (ICIs), sorafenib, and transarterial chemoembolization (TACE) treatment (all P<0.05).Consistently, TRIM genes showed the same influence in the external TCGA cohort. TRIM gene-based signatures were implicated in TIME and their copy-number alterations dynamically impacted the abundance of tumor-infiltrating immune cells.Conclusions: Our findings revealed that MID1, TRIM5, TRIM22, TRIM28, TRIM 31, TRIM37, TRIM38, TRIM47, and TRIM74 could serve as efficient prognostic biomarkers and therapeutic targets in HCC. The identified TRIM gene-based signatures could serve as important TIME mediators in HCC, potentially increasing immune treatment efficacy.

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Section: Discussionsupporting

confidence: 91%

Bioinformatics analysis of immune infiltrates and tripartite motif (TRIM) family genes in hepatocellular carcinoma

Cao¹,

Su²,

Peng³

et al. 2022

J Gastrointest Oncol

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“…Tissue-agnostic biomarkers such as tumour mutation burden (TMB) and MSI have been examined for cancer immunotherapy [57][58][59]. TMB has been utilised as a predictive biomarker in cancer immunotherapy in several studies [11,[60][61][62]. Our previous study demonstrated significant association of TMB with poor clinical outcomes in HCC patients [11].…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint molecules are regulated by transforming growth factor (TGF)-β1-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma

et al. 2021

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“…Because of its high speci city and can be recognized by immune cells, it is the target of personalized therapeutic cancer vaccines [36]. Previous studies have con rmed thatMUC16 is associated with TMB in hepatocellular carcinoma and gastric cancer [37,38]. MUC family proteins are highly related to MSI in colon cancer [39].…”

Section: Discussionmentioning

confidence: 99%

Expression signature, prognosis value, and immune characteristics of MUC1 identified by pan-cancer analysis

Zhang¹,

Huang²,

Liu³

et al. 2021

Preprint

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Background: Mucin 1 (MUC1) plays a major role in the occurrence and development of tumor by regulating the process of tumor cell proliferation, epithelial-mesenchymal transformation and epigenetics. However, the relationship between MUC1 expression and tumor prognosis and its role in tumor immunity is still worth exploring. Methods: MUC1 expression was analyzed via GTEx database and TCGA database. We used the Kaplan-Meier survival estimation method to evaluate the influence of MUC1 on tumor prognosis through the survival information from TGCA database. The correlations between MUC1 and immune cell infiltration, tumor microenvironment were investigated through TIMER algorithm and ESTIMATE. In addition, we used Spearman correlation test to examine the correlation between MUC1 and TMB, MSI. Spearman correlation test was also designed to predict the correlation between MUC1 and immune checkpoint genes, four methyltransferases. Further, Gene Set Enrichment Analysis was used to explore the potential mechanism of MUC1 in Adrenocortical carcinoma (ACC) and Liver hepatocellular carcinoma (LIHC). Results: Our study reported that MUC1 is highly expressed in most tumors, differing between cancer types. In most cancers, high expression of MUC1 means poor prognosis indicators, such as overall survival (OS), disease free survival (DSS), disease free survival (DFS) and progression free survival (PFS). MUC1 was positively correlated with infiltrating levels of B cells, CD4+ T cells and CD8+ T cells, dendritic cells, macrophages, neutrophils in LIHC, Prostate adenocarcinoma (PRAD) and Thyroid carcinoma (THCA). Besides, we reported that the expression of MUC1 correlated significantly with immune checkpoint gene, TMB and MSI and in most tumors. However, we found that MUC1 is negatively correlated with most immunotherapy-related indicators in BRCA and LUAD. The relationship between MUC1 and tumor neoantigens and DNA methylase is different in different tumors.In ACC and LIHC, MUC1 can promote the metabolism of many substances. MUC1 can inhibit amyotrophic lateral sclerosis, DNA replication, base excision repair, proteasome in ACC. Similarly, MUC1 inhibits axon guidance, the interaction of cytokine and cytokine receptor, focal adhesion, and endocytosis in LIHC. Conclusions: Our research demonstrates that MUC1 is correlated with prognosis and tumor-infiltrating immune cells, including those of B cells, CD8+ T cells, CD4+ T cells, dendritic cells, macrophages, neutrophils in different tumors. In addition, MUC1 is related to immune checkpoint gene, neoantigen, and some prognostic indicators of immunotherapy such as TMB and MSI, suggesting that MUC1 can also be invoked as a target and prognostic biomarker of immunotherapy. By analyzing the relationship between the expression of MUC1 and methyltransferase, we found that MUC1 regulates DNA methylation. Finally, we used GSEA to study the function of MUC1 in ACC and LIHC. Briefly, our study highlights the significance of MUC1 in the study of tumor immunity from the perspective of pan-cancer.

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Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis

Cited by 10 publications

References 15 publications

Bioinformatics analysis of immune infiltrates and tripartite motif (TRIM) family genes in hepatocellular carcinoma

Bioinformatics analysis of immune infiltrates and tripartite motif (TRIM) family genes in hepatocellular carcinoma

Immune checkpoint molecules are regulated by transforming growth factor (TGF)-β1-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma

Expression signature, prognosis value, and immune characteristics of MUC1 identified by pan-cancer analysis

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