Comprehensive Analysis of the Glycolysis-Related Gene Prognostic Signature and Immune Infiltration in Endometrial Cancer

Yang, Xiao; Li, Xingchen; Cheng, Yuan; Zhou, Jingyi; Shen, Boqiang; Zhao, Lijun; Wang, Jianliu

doi:10.3389/fcell.2021.797826

Cited by 11 publications

(10 citation statements)

References 43 publications

(39 reference statements)

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“…model and the Yao. model ( Yang et al, 2021 ; Chen et al, 2022 ). The nomogram with powerful and robust prediction performance has advantages over other clinicopathological features and models ( Figure 5C ).…”

Section: Resultsmentioning

confidence: 99%

A 13-Gene Signature Based on Estrogen Response Pathway for Predicting Survival and Immune Responses of Patients With UCEC

Tian

Liu

et al. 2022

Front. Mol. Biosci.

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Background: Accumulating evidence suggests that anti-estrogens have been effective against multiple gynecological diseases, especially advanced uterine corpus endometrial carcinoma (UCEC), highlighting the contribution of the estrogen response pathway in UCEC progression. This study aims to identify a reliable prognostic signature for potentially aiding in the comprehensive management of UCEC.Methods: Firstly, univariate Cox and LASSO regression were performed to identify a satisfying UCEC prognostic model quantifying patients’ risk, constructed from estrogen-response-related genes and verified to be effective by Kaplan-Meier curves, ROC curves, univariate and multivariate Cox regression. Additionally, a nomogram was constructed integrating the prognostic model and other clinicopathological parameters. Next, UCEC patients from the TCGA dataset were divided into low- and high-risk groups according to the median risk score. To elucidate differences in biological characteristics between the two risk groups, pathway enrichment, immune landscape, genomic alterations, and therapeutic responses were evaluated to satisfy this objective. As for treatment, effective responses to anti-PD-1 therapy in the low-risk patients and sensitivity to six chemotherapy drugs in the high-risk patients were demonstrated.Results: The low-risk group with a relatively favorable prognosis was marked by increased immune cell infiltration, higher expression levels of HLA members and immune checkpoint biomarkers, higher tumor mutation burden, and lower copy number alterations. This UCEC prognostic signature, composed of 13 estrogen-response-related genes, has been identified and verified as effective.Conclusion: Our study provides molecular signatures for further functional and therapeutic investigations of estrogen-response-related genes in UCEC and represents a potential systemic approach to characterize key factors in UCEC pathogenesis and therapeutic responses.

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Section: Resultsmentioning

confidence: 99%

A 13-Gene Signature Based on Estrogen Response Pathway for Predicting Survival and Immune Responses of Patients With UCEC

Tian

Liu

et al. 2022

Front. Mol. Biosci.

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“…Score, Cu. Score, the Wang’s sig, and the Yao’s sig ( Yang et al, 2021 ; Chen et al, 2022 ) and discovered that the AUC of OS for the Risk. Score is 0.753, which is significantly higher than that of other signatures ( Supplementary Figure S10F ).…”

Section: Resultsmentioning

confidence: 99%

A comprehensive analysis focusing on cuproptosis to investigate its clinical and biological relevance in uterine corpus endometrial carcinoma and its potential in indicating prognosis

Tian

Tan

et al. 2022

Front. Mol. Biosci.

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Cuproptosis, a novel copper-dependent cell death involving mitochondrial respiration, is distinct from other known death mechanisms, which inspires us to study further in uterine corpus endometrial carcinoma (UCEC). Herein, leveraging comprehensive data from TCGA-UCEC, we conducted transcriptional and genetic analyses of 13 recently identified cuproptosis genes. We discovered severe genetic instability of cuproptosis genes, extensive positive correlations among those genes with each other at the mRNA level, and their involvement in oncogenic pathways in UCEC samples. Next, WGCNA was performed to identify a potential module regulating cuproptosis, in which the hub genes, in addition to 13 cuproptosis genes, were drawn to construct a scoring system termed Cu. Score. Furthermore, its clinical and biological relevance and tumor immune landscape, genetic alterations, as well as predicted sensitivity of chemotherapy drugs in different Cu. Score subgroups had been discussed extensively and in detail. Additionally, univariate Cox and LASSO regression were performed to identify 13 cuproptosis-related prognostic genes to establish a prognostic signature, the Risk. Score. Integrating the Risk. Score and clinical parameters, we established a nomogram with excellent performance to predict the 1-/3-/5-year survival probabilities of UCEC patients. To conclude, we conducted a comprehensive analysis encompassing cuproptosis and developed a cuproptosis scoring system and a prognostic prediction model for UCEC, which may offer help with individualized assessment and treatment for UCEC patients from the perspective of a novel death mechanism.

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“…Glycolysis, also named the “Warburg effect”, acts as a core hallmark of cancer metabolism. It is now established that glycolysis contributes to tumor growth, drug resistance, and immune escape ( 35 – 37 ). For example, the glycolysis process was found to be remarkably upregulated in RCC samples, and its core regulatory genes PLOD1, PLOD2, and CD44 could promote the proliferation of renal cancer cells ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

N7-Methylguanosine Regulatory Genes Profoundly Affect the Prognosis, Progression, and Antitumor Immune Response of Hepatocellular Carcinoma

Zhou

Yang²,

Li³

et al. 2022

Front. Surg.

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BackgroundHepatocellular carcinoma (HCC) is a common abdominal cancer with poor survival outcomes. Although there is growing evidence that N7-methylguanosine (m7G) is closely associated with tumor prognosis, development, and immune response, few studies focus on this topic.MethodsThe novel m7G risk signature was constructed through the Lasso regression analysis. Its prognostic value was evaluated through a series of survival analyses and was tested in ICGC-LIRI, GSE14520, and GSE116174 cohorts. CIBERSORT, ssGSEA, and ESTIMATE methods were applied to explore the effects of the m7G risk score on tumor immune microenvironment (TIM). The GSEA method was used to evaluate the impacts of the m7G risk score on glycolysis, ferroptosis, and pyroptosis. The human protein atlas (HPA) database was used to clarify the histological expression levels of five m7G signature genes. The biofunctions of NCBP2 in hepatocellular cancer (HC) cells were confirmed through qPCR, CCK8, and transwell assays.ResultsFive m7G regulatory genes comprised the novel risk signature. The m7G risk score was identified as an independent prognostic factor of HCC and could increase the decision-making benefit of traditional prognostic models. Besides, we established a nomogram containing the clinical stage and m7G risk score to predict the survival rates of HCC patients. The prognostic value of the m7G model was successfully validated in ICGC and GSE116174 cohorts. Moreover, high m7G risk led to a decreased infiltration level of CD8+ T cells, whereas it increased the infiltration levels of Tregs and macrophages. The glycolysis and pyroptosis processes were found to be enriched in the HCC patients with high m7G risk. Finally, overexpression of NCBP2 could promote the proliferation, migration, and invasion of HC cells.ConclusionsThe m7G risk score was closely related to the prognosis, antitumor immune process, glycolysis, and malignant progression of HCC. NCBP2 has pro-oncogenic abilities, showing promise as a novel treatment target.

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Comprehensive Analysis of the Glycolysis-Related Gene Prognostic Signature and Immune Infiltration in Endometrial Cancer

Cited by 11 publications

References 43 publications

A 13-Gene Signature Based on Estrogen Response Pathway for Predicting Survival and Immune Responses of Patients With UCEC

A 13-Gene Signature Based on Estrogen Response Pathway for Predicting Survival and Immune Responses of Patients With UCEC

A comprehensive analysis focusing on cuproptosis to investigate its clinical and biological relevance in uterine corpus endometrial carcinoma and its potential in indicating prognosis

N7-Methylguanosine Regulatory Genes Profoundly Affect the Prognosis, Progression, and Antitumor Immune Response of Hepatocellular Carcinoma

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