Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

Li, Lijuan; Song, Shaohua; Fang, Xiaoling; Cao, Deliang

doi:10.1186/s12920-020-00852-4

Cited by 11 publications

(5 citation statements)

References 38 publications

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“… 56 Recently, ATF3 was reported in hepatocellular carcinoma as a novel cancer suppressor gene. 57 Our findings showed that ATF3 was one of the significantly up-regulated genes after treating cancer cells with celastrol, which could participate in the celastrol’s inhibitory effect on the growth of pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 57%

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Youns¹,

Askoura²,

Abbas³

et al. 2021

OTT

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Background Pancreatic cancer is one of the most serious and lethal human cancers with a snowballing incidence around the world. The natural product celastrol has also been widely documented as a potent anti-inflammatory, anti-angiogenic, and anti-oxidant. Purpose To elucidate the antitumor effect of celastrol on pancreatic cancer cells and its modulatory role on whole genome expression. Methods The antitumor activity of celastrol on a panel of pancreatic cancer cells has been evaluated by Sulforhodamine B assay. Caspase 3/7 and histone-associated DNA fragments assays were done for apoptosis measurement. Additionally, prostaglandin (PGE2) inhibition was evaluated. Moreover, a microarray gene expression profiling was carried out to detect possible key players that modulate the antitumor effects of celastrol on cells of pancreatic cancer. Results Our findings indicated that celastrol suppresses the cellular growth of pancreatic cancer cells, induces apoptosis, and inhibits PGE2 production. Celastrol modulated many signaling genes and its cytotoxic effect was mainly mediated via over-expression of ATF3 and DDIT3 , and down-expression of RRM2 and MCM4 . Conclusion The current study aims to be a starting point to generate a hypothesis on the most significant regulatory genes and for a full dissection of the celastrol possible effects on each single gene to prevent the pancreatic cancer growth.

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Section: Discussionmentioning

confidence: 57%

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Youns¹,

Askoura²,

Abbas³

et al. 2021

OTT

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“…5F lower panel). In addition we observed the downregulation of Atf3, a transcription factor whose the downregulation is associated with a poor tumor outcome [46] (Fig. 5F).…”

Section: By Using Upsetplot Representations To Identify Intersection ...mentioning

confidence: 75%

“…Atf3 is a gene known to play a crucial role in several biological processes, such as immune response regulation. It has been reported that its downregulation in macrophages is associated with a worse outcome in patients with hepatocellular carcinoma [46]. Atf3 was also shown to be downregulated in hematopoietic stem and progenitor cells during aging, and its expression restored after a parabiosis experiment with young mice [55].…”

Section: Discussionmentioning

confidence: 96%

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Beauséjour

Maggiorani

Lê

et al. 2023

Preprint

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Immune checkpoint inhibitors (ICI) invigorate immune cell functions and are effective against many cancer types. However, the potential of ICI may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of αPD-L1-based cancer immunotherapies is compromised by the accumulation of senescent cells in mice previously exposed to sublethal irradiation or injected with doxorubicin. Similarly, we observed that the efficacy of the combination of a αCTLA-4 antibody with radiotherapy is diminished in previously irradiated mice. In both models, resistance to immunotherapy was associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells by the injection of the senolytic drug ABT263, weeks before treatments, restored immune homeostasis within the tumor micro-environment (TME) and increased mice survival in both models. Using single-cell transcriptomic analysis, we observed that the injection of ABT263 reverses the exacerbated immunosuppressive profile of myeloid cells in the TME of previously irradiated mice. These myeloid cells, when purified from established tumors, were responsible for impaired CD8 T cell proliferation in vitro. Our study shows that cancer therapies, by inducing senescence, favor the formation of an immunosuppressive TME, which can alter the efficacy of ICI. The use of senolytic drugs before ICI may constitute an interesting pharmacological approach to improve the effectiveness of cancer immunotherapies.

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“…For example, SLC2A3 could act as a biomarker to determine prognosis and immune infiltration in gastric cancer by mediating glycolysis reprogramming (Yao et al, 2020). The stress response gene ATF3, has been shown to activate erastin-induced ferroptosis by repressing amino acid antiporter system Xc − (Wang et al, 2020) and could serve as a prognostic biomarker in hepatocellular carcinoma (Li et al, 2021). TXNIP has been implicated in ferroptosis in retinal cells (Singh et al, 2020), and its downregulation indicates poor prognosis in patients with clear cell renal cell carcinoma (Gao et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A Ferroptosis-Related Gene Signature Identified as a Novel Prognostic Biomarker for Colon Cancer

Wang

Lin

et al. 2021

Front. Genet.

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BackgroundColon cancer (CC) is a common gastrointestinal malignant tumor with high heterogeneity in clinical behavior and response to treatment, making individualized survival prediction challenging. Ferroptosis is a newly discovered iron-dependent cell death that plays a critical role in cancer biology. Therefore, identifying a prognostic biomarker with ferroptosis-related genes provides a new strategy to guide precise clinical decision-making in CC patients.MethodsAlteration in the expression profile of ferroptosis-related genes was initially screened in GSE39582 dataset involving 585 CC patients. Univariate Cox regression analysis and LASSO-penalized Cox regression analysis were combined to further identify a novel ferroptosis-related gene signature for overall survival prediction. The prognostic performance of the signature was validated in the GSE17536 dataset by Kaplan-Meier survival curve and time-dependent ROC curve analyses. Functional annotation of the signature was explored by integrating GO and KEGG enrichment analysis, GSEA analysis and ssGSEA analysis. Furthermore, an outcome risk nomogram was constructed considering both the gene signature and the clinicopathological features.ResultsThe prognostic signature biomarker composed of 9 ferroptosis-related genes accurately discriminated high-risk and low-risk patients with CC in both the training and validation datasets. The signature was tightly linked to clinicopathological features and possessed powerful predictive ability for distinct clinical subgroups. Furthermore, the risk score was confirmed to be an independent prognostic factor for CC patients by multivariate Cox regression analysis (p < 0.05). Functional annotation analyses showed that the prognostic signature was closely correlated with pivotal cancer hallmarks, particularly cell cycle, transcriptional regulation, and immune-related functions. Moreover, a nomogram with the signature was also built to quantify outcome risk for each patient.ConclusionThe novel ferroptosis-related gene signature biomarker can be utilized for predicting individualized prognosis, optimizing survival risk assessment and facilitating personalized management of CC patients.

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Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

Cited by 11 publications

References 38 publications

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

A Ferroptosis-Related Gene Signature Identified as a Novel Prognostic Biomarker for Colon Cancer

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