Hypoxia-Related Gene-Based Signature Can Evaluate the Tumor Immune Microenvironment and Predict the Prognosis of Colon Adenocarcinoma Patients

He, Xueling; Ding, Jianfeng; Cheng, Xiangdong; Xiong, Maoming

doi:10.2147/ijgm.s343216

Cited by 9 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To predict cancer, some scholars have used genes including SLC2A3 to construct models. A study constructed a hypoxia risk model using four hypoxia-related genes, TKTL1, SLC2A3, ALDOB, and ENO3, as a way to assess the tumor immune microenvironment and predict the overall survival of patients with colon adenocarcinoma (COAD), and thus develop hypoxia-targeted drugs for COAD patients (He et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis

Pan

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Introduction: Periodontitis is a chronic inflammatory oral disease that destroys soft and hard periodontal support tissues. Multiple cell death modes including apoptosis, necroptosis, pyroptosis, and ferroptosis play a crucial role in the pathogenicity of inflammatory diseases. This study aimed to identify genes associated with ferroptosis, necroptosis, and pyroptosis in different cells present in the periodontium of periodontitis patients.Methods: Gingival tissues’ mRNA sequencing dataset GSE173078 of 12 healthy control and 12 periodontitis patients’ and the microarray dataset GSE10334 of 63 healthy controls and 64 periodontitis patients’ were obtained from Gene Expression Omnibus (GEO) database. A total of 910 differentially expressed genes (DEGs) obtained in GSE173078 were intersected with necroptosis, pyroptosis, and ferroptosis-related genes to obtain the differential genes associated with cell death (DCDEGs), and the expression levels of 21 differential genes associated with cell death were verified with dataset GSE10334.Results: Bioinformatic analysis revealed 21 differential genes associated with cell death attributed to ferroptosis, pyroptosis, and necroptosis in periodontitis patients compared with healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that 21 differential genes associated with cell death were related to various cellular and immunological pathways including inflammatory responses, necroptosis, and osteoclast differentiation. Additionally, the single-cell RNA (scRNA) sequencing data GSE171213 of 4 healthy controls and 5 periodontitis patients’ periodontal tissue was analyzed to obtain cell clustering and cell types attributed to differential genes associated with cell death. We found that among 21 DCDEGs, SLC2A3, FPR2, TREM1, and IL1B were mainly upregulated in neutrophils present in the periodontium of periodontitis patients. Gene overlapping analysis revealed that IL-1B is related to necroptosis and pyroptosis, TREM1 and FPR2 are related to pyroptosis, and SLC2A3 is related to ferroptosis. Finally, we utilized the CIBERSORT algorithm to assess the association between DCDEGs and immune infiltration phenotypes, based on the gene expression profile of GSE10334. The results revealed that the upregulated SLC2A3, FPR2, TREM1, and IL1B were positively correlated with neutrophil infiltration in the periodontium.Discussion: The findings provide upregulated SLC2A3, FPR2, TREM1, and IL1B in neutrophils as a future research direction on the mode and mechanism of cell death in periodontitis and their role in disease pathogenicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis

Pan

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Frontiers in Genetics frontiersin.org 13 Inhibition of CD36 might prove beneficial in repressing metastasis spread, which demonstrated clinical practice potential (Enciu et al, 2018). ENO3, as a glycolysis and hypoxia-related gene, could predict the prognosis and immune landscape of colon cancer patients (Cui et al, 2021;He et al, 2021;Mao et al, 2022). ENO3 could promote CRC cell proliferation and migration by promoting glycolysis metabolism (Chen et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance and immune landscape of a fatty acid metabolism-related gene signature in colon adenocarcinoma

et al. 2022

View full text Add to dashboard Cite

Background: Fatty acid metabolism (FAM), as a hallmark of caner, plays important roles in tumor initiation and carcinogenesis. However, the significance of fatty acid metabolism-related genes in colon adenocarcinoma (COAD) are largely unknown.Methods: RNA sequencing data and clinical information were downloaded from the Cancer Genome Atlas (TCGA) cohort. Univariate and multivariate Cox regression analyses were utilized to construct a fatty acid metabolism-related gene signature. Kaplan-Meier survival and receiver operating characteristic (ROC) analyses were used to verify the performance of this signature. GEO datasets were applied to validate the signature. Maftools package was utilized to analyze the mutation profiles of this signature. Correlation between the risk signature and stemness scores was compared by RNA stemness score (RNAss). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set variation analysis (GSVA) were performed to explore the potential functions and signaling pathways. Immune landscape of the signature was explored by analyzing different immune cells infiltration, immune functions and microsatellite instability. A nomogram was constructed by combining the risk signature and multiple clinical factors. Expression levels and prognostic values of the risk genes were revealed in the cancer genome atlas and GEO databases. Moreover, the expression the risk genes were measured in cell lines using real time quantitative PCR (qRT-PCR).Results: Eight fatty acid metabolism-related genes (CD36, ENO3, MORC2, PTGR1, SUCLG2, ELOVL3, ELOVL6 and CPT2) were used to construct a risk signature. This signature demonstrated better prognostic value than other clinicopathological parameters, with AUC value was 0.734 according to the cancer genome atlas database. There was negative correlation between the riskscore and RNA stemness score. The patients in the high-risk group demonstrated higher infiltration of M0 macrophages, and less infiltration of activated CD4 memory T cells and Eosinophils. There were more MSI patients in the high-risk group than those in the low-risk group (38% vs. 30%). The risk scores of patients in the MSI group were slightly higher than those in the microsatellite stability group. Gene ontology, kyoto encyclopedia of genes and genomes and gene set variation analysis enrichment analyses showed that several metabolism-related functions and signaling pathways were enriched. A nomogram showed good predictive capability of the signature. Moreover, qRT-PCR revealed upregulated expression of ENO3, MORC2, SUCLG2 and ELOVL6, and downregulated expression of CPT2 in all examined colon adenocarcinoma cell lines.Conclusion: This study provided novel insights into a fatty acid metabolism-related signature in the prognosis an immune landscape of colon adenocarcinoma patients.

show abstract

“…Studies have shown that in a hypoxic tumor microenvironment, the immune checkpoints, including PD1, PD-L1 and CTLA 4, are upregulated, as are the immunosuppressive cells. In such a state, effector T cells are inhibited and suppressive cells, such as regulatory T cells and tumor-associated macrophages, are in an increased amount [ 27 ]. In our samples, intratumoral immune cells were present in variable amounts.…”

Section: Discussionmentioning

confidence: 99%

Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors

Herlea

Roşulescu

Calota³

et al. 2022

Medicina

View full text Add to dashboard Cite

Background and Objectives: GISTs are the most frequent type of mesenchymal neoplasm of the digestive tract. The prognosis is mainly determined by tumor dimensions, mitotic rate and location, but other less well-documented factors can influence evolution and survival. The immune microenvironment and checkpoint molecule expression were proven to impact the prognosis in different types of cancer. The aim of this study was to determine PD-L1 expression in GISTs and to evaluate the level of intratumoral immune infiltration in relation to prognostic variables and survival. Materials and Methods: Sixty-five GISTs diagnosed in the same institution between 2015 and 2018 were immunohistochemically tested for PD-L1 and evaluated using CPS. Immune cells were emphasized, with CD3, CD4, CD8, CD20 and CD68 antibodies and quantified. All data were processed using statistical tools. Results: The median age was 61 years (range, 28–78) and 36 patients (55.4%) were males. The location of the tumors was predominantly gastric (46%), followed by the small bowel (17%) and colorectal (6%). In addition, 11% were EGISTs and 20% were secondary tumors (11% metastases and 9% local recurrences). PD-L1 had a variable expression in tumor and inflammatory cells, with a CPS ranging from 0 to 100. Moreover, 64.6% of cases were PD-L1 positive with no significant differences among categories of variables, such as the age and the sex of the patient, tumor location, the primary or secondary character of the tumor, dimensions, mitotic rate, the risk of disease progression and tumor cell type. Immune cells had a variable distribution throughout the tumors. CD3+ lymphocytes were the most frequent type. CD20+ cells were identified in a larger number in tumors ≤5 cm (p = 0.038). PD-L1-positive tumors had a higher number of immune cells, particularly CD3+, CD20+ and CD68+, in comparison to PD-L1-negative ones (p = 0.032, p = 0.051, p = 0.008). Epithelioid and mixed cell-type tumors had a higher number of CD68+ cells. Survival was not influenced by PD-L1 expression; instead, it was decreased in multifocal tumors (p = 0.0001) and in cases with Ki67 ≥ 50% (p = 0.008). Conclusions: PD-L1-positive expression and the presence of different immune cell types, in variable quantities, can contribute to a better understanding of the complex interactions between tumor cells and the microenvironment, with a possible therapeutic role in GISTs.

show abstract

Hypoxia-Related Gene-Based Signature Can Evaluate the Tumor Immune Microenvironment and Predict the Prognosis of Colon Adenocarcinoma Patients

Cited by 9 publications

References 33 publications

Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis

Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis

Prognostic significance and immune landscape of a fatty acid metabolism-related gene signature in colon adenocarcinoma

Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors

Contact Info

Product

Resources

About