A Novel Glycolysis and Hypoxia Combined Gene Signature Predicts the Prognosis and Affects Immune Infiltration of Patients with Colon Cancer

Mao, Guochao; Wu, Jianhua; Cui, Hanxiao; Dai, Luyao; Ma, Li; Zhou, Zhangjian; Liang, Baobao; Zhang, Shuqun; Lin, Shuai

doi:10.2147/ijgm.s351831

Cited by 4 publications

(5 citation statements)

References 53 publications

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“…Furthermore, ENO3 may have a unique function in promoting glycolysis in tumor cells. To date, several sequencing-based studies have reported that ENO3 is involved in glycolysis and colorectal or colon cancer and that elevated ENO3 promotes ATP production or glycolysis under hypoxic conditions [ 27 , 54 ]. Furthermore, genome analysis using the Gene Expression Omnibus database revealed that ENO3 is involved in glycolysis regulation; LASSO Cox analysis revealed that ENO is associated with prognosis [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…Enolase 3 (ENO3) is a β -enolase that regulates striated muscle development [ 26 ]. Genomic analysis revealed that ENO3 is associated with the risk of colon cancer and that it is involved in the regulation of glycolysis [ 27 ]. Elevated levels of glycolysis result in the activation of inflammatory pathways [ 28 ], which are also involved in tumor progression [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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LINC00174 Promotes Colon Cancer Progression by Regulating Inflammation and Glycolysis by Targeting the MicroRNA-2467-3p/Enolase 3 Axis

Xu,

Lin,

Chen

et al. 2023

Mediators of Inflammation

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Objective. To elucidate the mechanism by which LINC00174 promotes colon cancer progression by targeting the microRNA-2467-3p (miR-2467-3p)/enolase 3 (ENO3) axis to regulate inflammation and glycolysis. Methods. The expression of LINC00174 and ENO3 in colon cancer tissues, its relationship with survival rate, and correlation were analyzed using bioinformatic analysis. The effects of LINC00174 overexpression and silencing on the biological behavior of and inflammation in colon cancer cells were analyzed via transfection experiments. The target relationships between miR-2467-3p or LINC00174 and ENO3 were verified using sequence prediction and the dual-luciferase reporter assay, respectively. Furthermore, LINC00174- and/or miR-2467-3p-overexpressing cells were prepared to determine the effects on ENO3 protein levels and glycolysis. Finally, the effects of LINC00174 and/or miR-2467-3p overexpression on colon cancer, ENO3 protein levels, and inflammation were analyzed using a tumor-bearing mice model. Results. LINC00174 and ENO3 were overexpressed and associated with a lower survival rate. LINC00174 was positively correlated with ENO3 in colon cancer tissues. Furthermore, the overexpression of LINC00174 in colon cancer cell lines promoted the proliferation, migration, and invasion of colon cancer cells and inflammation but inhibited apoptosis. The overexpression of miR-2467-3p inhibited ENO3 protein levels, which was attenuated via LINC00174 overexpression. Furthermore, it inhibited the biological behavior of and inflammation and glycolysis in colon cancer cells and blocked their LINC00174-induced promotion. Moreover, using animal experiments, the regulatory effects of LINC00174 on tumor growth, ENO3 protein levels, and inflammation via miR-2467-3p were confirmed. Conclusion. LINC00174 promotes the glycolysis, inflammation, proliferation, migration, and invasion of colon cancer cells and inhibits apoptosis. The cancer-promoting mechanism of LINC00174 is related to targeting miR-2467-3p to promote ENO3 protein levels.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LINC00174 Promotes Colon Cancer Progression by Regulating Inflammation and Glycolysis by Targeting the MicroRNA-2467-3p/Enolase 3 Axis

Xu,

Lin,

Chen

et al. 2023

Mediators of Inflammation

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“…STC2 is a glycoprotein hormone that promotes tumor development and invasion in several human malignancies. Mao et al showed that STC2 is a potential biomarker for tumor behavior among colorectal cancer patients (44) and a GSEA analysis study reported that STC2 is linked to HNSCC cell growth (45). STC2 is also associated with lymph node metastasis in esophageal cancer patients (46).…”

Section: Discussionmentioning

confidence: 99%

A Novel Immune-Related Gene Signature to Identify the Tumor Microenvironment and Prognose Disease Among Patients With Oral Squamous Cell Carcinoma Patients Using ssGSEA: A Bioinformatics and Biological Validation Study

et al. 2022

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Oral squamous cell carcinoma (OSCC) is the most invasive oral malignancy in adults and is associated with a poor prognosis. Accurate prognostic models are urgently needed, however, knowledge of the probable mechanisms behind OSCC tumorigenesis and prognosis remain limited. The clinical importance of the interplay between the immune system and tumor microenvironment has become increasingly evident. This study explored immune-related alterations at the multi-omics level to extract accurate prognostic markers linked to the immune response and presents a more accurate landscape of the immune genomic map during OSCC. The Cancer Genome Atlas (TCGA) OSCC cohort (n = 329) was used to detect the immune infiltration pattern of OSCC and categorize patients into two immunity groups using single-sample gene set enrichment analysis (ssGSEA) and hierarchical clustering analysis. Multiple strategies, including lasso regression (LASSO), Cox proportional hazards regression, and principal component analysis (PCA) were used to screen clinically significant signatures and identify an incorporated prognosis model with robust discriminative power on the survival status of both the training and testing set. We identified two OSCC subtypes based on immunological characteristics: Immunity-high and immunity low, and verified that the categorization was accurate and repeatable. Immunity_ high cluster with a higher immunological and stromal score. 1047 differential genes (DEGs) integrate with immune genes to obtain 319 immue-related DEGs. A robust model with five signatures for OSCC patient prognosis was established. The GEO cohort (n = 97) were used to validate the risk model’s predictive value. The low-risk group had a better overall survival (OS) than the high-risk group. Significant prognostic potential for OSCC patients was found using ROC analysis and immune checkpoint gene expression was lower in the low-risk group. We also investigated at the therapeutic sensitivity of a number of frequently used chemotherapeutic drugs in patients with various risk factors. The underlying biological behavior of the OSCC cell line was preliminarily validated. This study characterizes a reliable marker of OSCC disease progression and provides a new potential target for immunotherapy against this disease.

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“…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

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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.

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A Novel Glycolysis and Hypoxia Combined Gene Signature Predicts the Prognosis and Affects Immune Infiltration of Patients with Colon Cancer

Cited by 4 publications

References 53 publications

LINC00174 Promotes Colon Cancer Progression by Regulating Inflammation and Glycolysis by Targeting the MicroRNA-2467-3p/Enolase 3 Axis

LINC00174 Promotes Colon Cancer Progression by Regulating Inflammation and Glycolysis by Targeting the MicroRNA-2467-3p/Enolase 3 Axis

A Novel Immune-Related Gene Signature to Identify the Tumor Microenvironment and Prognose Disease Among Patients With Oral Squamous Cell Carcinoma Patients Using ssGSEA: A Bioinformatics and Biological Validation Study

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

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