IMPDH1, a prognostic biomarker and immunotherapy target that correlates with tumor immune microenvironment in pan-cancer and hepatocellular carcinoma

Liu, Chengdong; Zhang, Wanli; Zhou, Xiaohan; Liu, Li

doi:10.3389/fimmu.2022.983490

Cited by 7 publications

(3 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This feedback mechanism also results in a positive correlation between the expression of immune-stimulatory genes and immune-inhibitory genes. Therefore, as our previous work has shown [ 17 ], molecules that have a significant impact on the TIME are likely to be positively associated with both immunosuppressive and immune-activating cells and genes. In general, manipulation of the TIME can serve as a useful strategy for combating resistance to immune checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 86%

KNSTRN, a Poor Prognostic Biomarker, Affects the Tumor Immune Microenvironment and Immunotherapy Outcomes in Pan-Cancer

et al. 2023

Self Cite

View full text Add to dashboard Cite

Kinetochore-localized astrin- (SPAG5-) binding protein (KNSTRN) is mainly involved in mitosis. Somatic mutations in KNSTRN are known to lead to the occurrence and development of certain tumors. However, the role of KNSTRN in the tumor immune microenvironment (TIME) as a tumor prognostic biomarker and potential therapeutic target has not been clarified. Accordingly, in this study, we aimed to investigate the role of KNSTRN in the TIME. mRNA expression, cancer patient prognosis, and correlations between KNSTRN expression and immune component infiltration were analyzed using Genotype-Tissue Expression, The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Human Protein Atlas, ImmuCellAI, TIMER2.0, and KM-Plotter. The Genomics of Drug Sensitivity in Cancer database was used to evaluate the relationship between KNSTRN expression and the half maximal inhibitory concentration (IC50) of several anticancer drugs, and gene set variation analysis was performed. Data were visualized using R version 4.1.1. KNSTRN expression was upregulated in the majority of cancers and was associated with a worse prognosis. Additionally, KNSTRN expression was highly correlated with the infiltration of multiple immune components in the TIME and was related to a poor prognosis in tumor patients receiving immunotherapy. KNSTRN expression was also positively correlated with the IC50 of various anticancer drugs. In conclusion, KNSTRN may be a significant prognostic biomarker and promising target for oncotherapy in numerous cancers.

show abstract

Section: Discussionmentioning

confidence: 86%

KNSTRN, a Poor Prognostic Biomarker, Affects the Tumor Immune Microenvironment and Immunotherapy Outcomes in Pan-Cancer

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…High expression of IMPDH1 is associated with poor prognosis of HCC patients and may serve as a potential target for immunotherapy. [66] S100A9 is a key oncogene in HCC progression, and its expression level is negatively correlated with the prognosis of patients. [67] Moreover, SLC16A3, and SLC1A5 have also been confirmed to be prognostic targets in HCC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of LRRC1 in hepatocellular carcinoma and construction of relevant prognostic model

Cai¹,

Wu²,

Shen

et al. 2023

Medicine

View full text Add to dashboard Cite

This study aimed to elucidate the prognostic value of the leucine rich repeat containing 1 (LRRC1) gene in hepatocellular carcinoma (HCC) and to determine the effects of high and low LRRC1 expression on mutation and immune cell infiltration. We downloaded HCC mRNA-seq expression and clinical data from University of California Santa Cruz Xena. The expression of LRRC1 was compared between HCC tumor and normal samples. Tumor samples were divided according to high and low LRRC1 expression. Differentially expressed genes between the 2 groups were identified, and function, mutation, and immune cell infiltration were analyzed. Genes associated with immune cells were identified using weighted gene co-expression network analysis, and transcription factors of these genes were predicted. Moreover, a prognostic model was developed and its performance was evaluated. The expression of LRRC1 was upregulated in HCC tissues, and this indicated a poor prognosis for patients with HCC. Differentially expressed genes between high and low LRRC1 expression were significantly enriched in pathways associated with cancer, amino acid metabolism, carbohydrate metabolism, and the immune system. We identified 15 differentially infiltrated immune cells between tumors with high and low LRRC1 expression and 14 of them correlated with LRRC1 gene expression. Weighted gene co-expression network analysis identified 83 immune cell-related genes, 27 of which had prognostic value. Cyclic AMP-response element binding protein regulated annexin A5, matrix metallopeptidase 9, and LRRC1 in the transcription factor regulatory network. Finally, a prognostic model composed of 7 genes were generated, which could accurately predict the prognosis of HCC patients. The LRRC1 gene might serve as a potential immune-associated prognostic biomarker for HCC.

show abstract

“…Some articles have further used cell lines to verify their analysis in vitro (35,36). Studies based on in vitro and in vivo experiments primarily involve patient samples and HCC cell lines (37)(38)(39). However, there have been few in vivo studies on m6A modi cation in the area of biologically engineered mice models.…”

Section: Discussionmentioning

confidence: 99%

Identification of METTL3 as a myeloid-related prognosis biomarker in hepatocellular carcinoma using bioinformatics analysis and engineered mice model

Wang

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related mortality, ranking third in this regard. The epigenetic regulation of RNA N6-methyladenosine (m6A) modification in HCC has garnered considerable attention. This study utilized bioinformatics analysis and biologically engineered mice models to explore the immune and prognostic role of m6A modification in HCC. Methods We systematically analyzed genetic alterations, expression patterns, signaling pathways, prognostic features, and immunotherapy efficacy of the 21 m6A regulators in HCC as obtained from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO, GSE14520, GSE76427), and International Cancer Genome Consortium (IGCG) database; Unsupervised clustering, gene set variation analysis (GSVA), LASSO-COX regression, multivariate Cox regression, Nomogram, receiver operating characteristic (ROC) analysis, TIMER 2.0 and ImmuCellAI were used to perform the above analysis. Our analysis was verified with Mettl3F/FAlbumin-cre (liver-specific knockout, LKO) mice to establish a chemo-induced HCC model. The tumor immune microenvironment was analyzed with immunohistochemistry, immunofluorescence staining, and flow cytometry. Results The genetic alteration of the m6A modification gene set exhibited a correlation with reduced progression-free survival, diminished abundance of macrophage cells, and a lower score for immune cell infiltration. The cluster characterized by lower expression of the m6A gene set was linked to a more favorable overall survival (OS) and immune signaling, including IL2-STAT5, IL6-STAT3, IFN-gamma, and IFN-alpha signaling. Notably, the cluster with higher expression of m6A was associated with a higher homologous recombination deficiency (HRD) score and tumor mutational burden (TMB) score. Results of LASSO COX and the nomogram model underscored the significant contribution of METTL3 in the prognosis and ICB therapy of HCC. The results of Mettl3 LKO mice confirmed that Mettl3 LKO acted as a "rheostat" in the progression of HCC by regulating the mouse liver's myeloid-related innate and adaptive immune landscape. Conclusions In this study, we characterized the genetic, immune, and clinic landscape of the m6A gene set in HCC development and unveiled METTL3 as a molecular biomarker in epigenetic-related progress and ICB therapy of HCC from both informatics database analysis and engineered mice model.

show abstract

IMPDH1, a prognostic biomarker and immunotherapy target that correlates with tumor immune microenvironment in pan-cancer and hepatocellular carcinoma

Cited by 7 publications

References 61 publications

KNSTRN, a Poor Prognostic Biomarker, Affects the Tumor Immune Microenvironment and Immunotherapy Outcomes in Pan-Cancer

KNSTRN, a Poor Prognostic Biomarker, Affects the Tumor Immune Microenvironment and Immunotherapy Outcomes in Pan-Cancer

Prognostic significance of LRRC1 in hepatocellular carcinoma and construction of relevant prognostic model

Identification of METTL3 as a myeloid-related prognosis biomarker in hepatocellular carcinoma using bioinformatics analysis and engineered mice model

Contact Info

Product

Resources

About