Nucleophosmin 1 is a prognostic marker of gastrointestinal cancer and is associated with m6A and cuproptosis

Liu, Xusheng; Liu, Chao; Zeng, Jing; Zeng, Dao-Bing; Chen, Yijia; Fan, Timothy M.; Gao, Yan; Liu, Xiaoyu; Zhang, Yaohua; Pei, Zhijun

doi:10.3389/fphar.2022.1010879

Cited by 8 publications

(5 citation statements)

References 60 publications

(69 reference statements)

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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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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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“…As described in an excellent review (24), several studies have reported that the expression of NPM1 is elevated in several cancers, including Ewing sarcoma, Gleason 4 pT3B prostate, colorectal, head-neck, kidney, leukemia, liver, lymphoma, renal, sarcoma, and gastrointestinal (88)(89)(90)(91)(92). We extended these results by analyzing the TCGA database for NPM1 expression in various tumors using TIMER2.0, an online tool to determine gene expression differences between cancer tissues and their normal counterparts (http://timer.cistrome.org/).…”

Section: Cancer Npm1 and Targetingmentioning

confidence: 99%

Nucleophosmin Plays a Role in Repairing DNA Damage and Is a Target for Cancer Treatment

Sekhar

Freeman

2023

Cancer Research

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Nucleophosmin (NPM1) is frequently mutated in acute myeloid leukemia, and NPM1 expression is elevated in several cancer types. NPM1 is a multifunctional oligomeric protein involved in numerous cellular functions that include participating in liquid-liquid phase separation, ribosome biogenesis, chaperoning of histones, and modulation of transcription. In this review, we discuss the underappreciated role of NPM1 in DNA damage repair, specifically Polη-mediated translesion synthesis, base excision, and homologous recombination and highlight the therapeutic potential of NPM1 targeting in cancer treatment.

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“…Nucleophosmin 1 (NPM1) is a protein transported between nucleus and cytoplasm and is the most studied protein in blood system diseases [ 44 ]. NPM1 expression is higher in ESCA patients than in healthy people, and higher expression is associated with poorer outcomes [ 45 ] (Table 1 ). NPM1 is thought to affect the progression of cuproptosis by changing copper concentration.…”

Section: Cuproptosis In Cancersmentioning

confidence: 99%

Role of cuproptosis in understanding diseases

Cao,

Wang,

Sun

et al. 2023

Human Cell

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Cell death is involved in a wide range of physiological and pathological processes. Recently, the term “cuproptosis” was coined to describe a novel type of cell death. This type of cell death, characterized by copper accumulation and proteotoxic stress, is a copper-dependent manner of death. Despite the progress achieved toward a better understanding of cuproptosis, mechanisms and related signaling pathways in physiology and pathology across various diseases remain to be proved. This mini review summarizes current research on cuproptosis and diseases, providing insights into prospective clinical therapies via targeting cuproptosis.

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Nucleophosmin 1 is a prognostic marker of gastrointestinal cancer and is associated with m6A and cuproptosis

Cited by 8 publications

References 60 publications

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

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

Nucleophosmin Plays a Role in Repairing DNA Damage and Is a Target for Cancer Treatment

Role of cuproptosis in understanding diseases

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