Comprehensive Analysis of Hexokinase 2 Immune Infiltrates and m6A Related Genes in Human Esophageal Carcinoma

Liu, Xusheng; Liu, Jiamin; Chen, Yijia; Li, Fuyan; Wu, Ruimin; Fan, Timothy M.; Zeng, Dao-Bing; Li, Wei; Zhou, Hong; Gao, Yan; Pei, Zhijun

doi:10.3389/fcell.2021.715883

Cited by 10 publications

(7 citation statements)

References 58 publications

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“…So far as the present conclusions are concerned, the differences in the correlation between the three separate scores might depict a conceptual map formed by immune and stromal cells in various malignancies, thus explaining the differential role of NCAPG2 in the prognosis of patients with diverse tumors. Targeting immune checkpoint genes like PD-1 and PD-L1, immune checkpoint blockade is currently among the mainstream immunotherapies (47,48). The present study found that NCAPG2 displayed a significant correlation with ICI-related genes in most cancers, with a predominantly positive correlation.…”

Section: Discussionsupporting

confidence: 50%

NCAPG2 could be an immunological and prognostic biomarker: From pan-cancer analysis to pancreatic cancer validation

Wang

Zhou

et al. 2023

Front. Immunol.

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More recently, NCAPG2 has emerged as an intrinsically essential participant of the condensin II complex involved in the process of chromosome cohesion and stabilization in mitosis, and its position in particular tumours is now being highlighted. Simultaneously, the genetic properties of NCAPG2 hint that it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. Yet, at present, this recognition remains merely superficial and there is a lack of more detailed studies to explore the underlying pathogenesis. To meet this need, the current study was undertaken to comprehensively elucidate the potential functions of NCAPG2 in pan-cancer, based on a combination of existing databases like TCGA and GTEx. NCAPG2 was identified to be overexpressed in almost every tumor and to exhibit significant prognostic and diagnostic efficacy. Furthermore, the correlation between NCAPG2 and selected immune features, namely immune cell infiltration, immune checkpoint genes, TMB, MSI, etc. also indicates that NCAPG2 could potentially be applied in guidance of immunotherapy. Subsequently, in pancreatic cancer, this study further clarified the utility of NCAPG2 that downregulation of its expression could result in reduced proliferation, invasion and metastasis of pancreatic cancer cells, among such phenotypical changes, the epithelial-mesenchymal transition disruption could be at least one of the possible mechanisms raising or enhancing tumorigenesis. Taken above, NCAPG2, as a member of pan-oncogenes, would serve as a biomarker and potential therapeutic target for a range of malignancies, sharing new insights into precision medicine.

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Section: Discussionsupporting

confidence: 50%

NCAPG2 could be an immunological and prognostic biomarker: From pan-cancer analysis to pancreatic cancer validation

Wang

Zhou

et al. 2023

Front. Immunol.

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“…The signi cant association between HK2 and T cells have been con rmed by several studies. For example HK2 is involved in tumor immune in ltration and m6A modi cation in ESCA [32]. It is noteworthy that HK3 also has the strongest correlation with tumor immunity, indicating that HK3 may serve as a new marker of tumor immunity.…”

Section: Discussionmentioning

confidence: 97%

Identification of the key roles of different hexokinases on the diagnosis, prognosis, tumor immunity, drug response: evidence from pan-cancer analysis and construction prognostic HKs signatures

Shang

Qiu

Wang

et al. 2023

Preprint

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Background Metabolic reprogramming is a key feature of cancer cells and is considered a new hallmark of cancer. With our increasing understanding and appreciation of tumor biology and metabolic complexity, targeting or regulating the expression of certain key metabolic enzymes of metabolic reprogramming may be important strategies for tumor therapy. Glycolysis is an essential part of the complex network of glucose metabolism, and hexokinases (HKs) are the key factors of the glycolysis pathway. Although HKs have also received attention in tumors, their roles in tumors are still not fully and systematically explored, particularly in immunization.Methods Through using multiple online datasets, including the TCGA database, Genecards database, CellMiner database, and Deepscreening database, and combining multiple algorithms, the association of HKs with prognosis, Tumor microenvironment (TME), Tumor immunity, and drug sensitivity were investigated. HKs were also evaluated for their prognostic relevance to specific tumor types and their synergistic effects by constructing prognostic HKs signatures. In particular, the deep learning algorithm predicted the active molecules binding to HKs.Results Cox and survival analysis suggested that HKs were significant factors influencing tumor progression. HKs expression levels strongly correlated with TME, RNAss, and Tumor immunity. Their influences varied in diverse tumors or some specific tumor types. In addition, the relationship between gene expression of HKs and drug sensitivity was investigated, and the results suggested the potential of targeting HKs, especially HKDC1 to improve drug resistance. Furthermore, a validation screen of drug prediction and molecular docking obtained several molecules targeting HKs. Finally, the roles of HKs were confirmed in Brain Lower Grade Glioma (LGG) and Acute Myeloid Leukemia (LAML) by constructing the HKs signatures, further, their homogeneity and heterogeneity were elaborated.Conclusion Our systematic study revealed the significant roles of HKs in tumorigenesis and metastasis, as well as their impact and diverse correlations on tumor immune and metabolic activity. The clinical application of HKs is a viable target and offers the new clinical prospects, especially in the development of personalized medicines for the treatment of LGG and LAML.

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“…And, abnormal glycosylation is also considered an indispensable part of the carcinogenesis process ( Ni et al, 2014 ), including BLCA. The research on protein modification and tumor heterogeneity, as well as the prediction of immunotherapy efficacy such as ICB, remains a hot topic in many cancers ( Liu et al, 2021 ; Liu et al, 2022 ). Therefore, our research was dedicated to deeply exploring the association between glycosylation and BLCA, with the goal of accurately predicting prognosis and individualized guidance for treatment of BLCA.…”

Section: Discussionmentioning

confidence: 99%

A glycosylation risk score comprehensively assists the treatment of bladder neoplasm in the real-world cohort, including the tumor microenvironment, molecular and clinical prognosis

Liu,

He,

Zhou

et al. 2023

Front. Pharmacol.

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Background: Bladder cancer is a common urological cancer associated high significant morbidity and mortality rates. Immunotherapy has emerged as a promising treatment option, although response rates vary among patients. Glycosylation has been implicated in tumorigenesis and immune regulation. However, our current comprehensive understanding of the role of glycosylation in bladder cancer and its clinical implications is limited.Methods: We constructed a training cohort based on the downloaded TCGA-BLCA dataset, while additional datasets (Xiangya cohort, GSE32894, GSE48075, GSE31684, GSE69795 and E-MTAB-1803) from Xiangya hospital, GEO and ArrayExpress database were obtained and used as validation cohorts. To identify glycosylation-related genes associated with prognosis, univariate Cox regression and LASSO regression were performed. A Cox proportional hazards regression model was then constructed to develop a risk score model. The performance of the risk score was assessed in the training cohort using Kaplan-Meier survival curves and ROC curves, and further validated in multiple validation cohorts.Results: We classified patients in the training cohort into two groups based on glycosylation-related gene expression patterns: Cluster 1 and Cluster 2. Prognostic analysis revealed that Cluster 2 had poorer survival outcomes. Cluster 2 also showed higher levels of immune cell presence in the tumor microenvironment and increased activation in key steps of the cancer immune response cycle. We developed an independent prognostic risk score (p < 0.001) and used it to construct an accurate prognostic prediction nomogram. The high glycosylation risk score group exhibited higher tumor immune cell infiltration, enrichment scores in immune therapy-related pathways, and a tendency towards a basal subtype. Conversely, the low-risk score group had minimal immune cell infiltration and tended to have a luminal subtype. These findings were consistent in our real-world Xiangya cohort.Conclusion: This multi-omics glycosylation score based on these genes reliably confirmed the heterogeneity of bladder cancer tumors, predicted the efficacy of immunotherapy and molecular subtypes, optimizing individual treatment decisions.

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Comprehensive Analysis of Hexokinase 2 Immune Infiltrates and m6A Related Genes in Human Esophageal Carcinoma

Cited by 10 publications

References 58 publications

NCAPG2 could be an immunological and prognostic biomarker: From pan-cancer analysis to pancreatic cancer validation

NCAPG2 could be an immunological and prognostic biomarker: From pan-cancer analysis to pancreatic cancer validation

Identification of the key roles of different hexokinases on the diagnosis, prognosis, tumor immunity, drug response: evidence from pan-cancer analysis and construction prognostic HKs signatures

A glycosylation risk score comprehensively assists the treatment of bladder neoplasm in the real-world cohort, including the tumor microenvironment, molecular and clinical prognosis

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