Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47

Lee, Yong Jae; Nam, Eun Ji; Kim, Sung Hoon; Kim, Young-Tae; Itkin-Ansari, Pamela; Kim, Sang Wun

doi:10.3390/cancers14122903

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…The standard approach for treating patients with advanced epithelial ovarian cancer remains cytoreductive surgery and platinumbased chemotherapy [2]. Although the majority of patients with advanced stage disease (i.e., stage III-IV) initially respond to front-line therapy consisting of cytoreductive surgery and platinum-based chemotherapy, 60-80% of patients with advanced disease will experience recurrence [3]. In most cases, cancer recurrence occurs at progressively shorter intervals, and patients eventually develop drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Assessment of lncRNA biomarkers based on NETs for prognosis and therapeutic response in ovarian cancer

Wang,

Liang,

Meng

et al. 2024

Preprint

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Background: Ovarian cancer (OC) usually progresses rapidly associated with high mortality, while a reliable clinical factor for OC patients to predict prognosis is currently lacking. Recently, the pathogenic role of neutrophils releasing neutrophil extracellular traps (NETs) in various cancers including OC has gradually been recognized. The study objective was to determine whether NETs-related biomarkers can be used to accurately predict the prognosis and guide clinical decision-making in OC. Methods: In this research, we utilized both univariate and multivariate Cox regression analysis to detect important prognostic characteristics. A set of six lncRNAs related to NETs was used to build a model, and the feature selection was performed using the LASSO regression algorithm. The model's predictive capability was evaluated using Kaplan-Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, as well as univariate and multivariate Cox analyses. In order to obtain a better understanding of the fundamental processes of the predictive model, we performed an analysis of gene ontology (GO) terms, enrichment analyses of KEGG pathways, and Gene set enrichment analysis (GSEA). Furthermore, we examined the mutation status of every gene in every sample using cascade diagrams and explored the correlation between tumor mutation load, rate of survival, and the model. In addition, we conducted a comparison of immune functions, the expression of targeted immune checkpoints, and the sensitivity to chemotherapeutic drugs in both low- and high-risk groups. Ultimately, we confirmed the predictive significance of our model by analyzing data from test sets as well as ovarian cancer cells and tissues acquired from our institution. Results: We built a model consisting of six lncRNAs associated with NETs, specifically GAS5, GBP1P1, LINC00702, LINC01933, LINC02362, and ZNF687-AS1. The ROC curve was used to evaluate the predictive performance of the models and compared with traditional clinicopathological features. The analysis of the GO process indicated that the predominant category was molecular function associated with antigen binding, along with several biological processes related to the immune system. Furthermore, variations were noted in the manifestation of transcription regulators linked to immune response, including the facilitation of inflammation, cytotoxic capabilities, and regulatory points. In addition, we made predictions for the IC50 values of chemotherapeutic drugs (bexarotene, bicalutamide, embelin, GDC0941, and thapsigargin) in both high-risk and low-risk groups. According to the findings, low-risk patients exhibited elevated IC50 values for all five medications. In the end, we confirmed the strength of the risk model by testing it on OC cells and tissues along with clinical data. Conclusion: We established a NETs-related lncRNA risk model, which has the potential to predict the prognosis and clinical response of OC patients. In the short term, the model could assist healthcare professionals in identifying patients who require individualized therapeutic approaches, including those who might gain advantages from immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Assessment of lncRNA biomarkers based on NETs for prognosis and therapeutic response in ovarian cancer

Wang,

Liang,

Meng

et al. 2024

Preprint

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“…High levels of ID1 and/or ID3 are associated with a variety of cancers, including ovarian cancer, thyroid cancer, and glioblastoma [1][2][3] . ID proteins promote DNA replica�on and cell survival and can subvert KRASinduced senescence 4 .…”

Section: Introduc�onmentioning

confidence: 99%

“…ID proteins inhibit cell differen�a�on, promote DNA replica�on and cell survival, and can subvert KRAS-induced senescence 1 . High levels of ID1 and/or ID3 are associated with a variety of cancers, including ovarian cancer, thyroid cancer, and glioblastoma [2][3][4] .…”

mentioning

confidence: 99%

Bone Morphogenetic Protein (BMP) signaling upregulates expression of ID1 and ID3 in pancreatitis and pancreatic ductal adenocarcinoma

Raghunathan,

Scully,

Wehrmaker

et al. 2023

Preprint

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Identification of biological modulators of pancreatic ductal adenocarcinoma (PDAC) initiation and progression are of critical importance as it remains one of the deadliest cancers. We have previously shown that ID1 and ID3 are highly expressed in human PDAC and function to repress expression of E47 target genes involved in acinar cell differentiation and quiescence. More recently, mining of large bulk RNA-seq and single-cell RNA-seq (scRNA-seq) datasets has associated high expression of ID1 with poor PDAC patient survival. Here, we report that BMP2 signaling in human PDAC cells upregulates expression of ID1 and ID3 while treatment with Noggin, an endogenous BMP antagonist, or with DMH1, a selective inhibitor of the BMP receptor, ALK2, reduced expression of ID1/ID3. BMP signaling, working via the canonical pathway involving phosphorylation of SMAD1/5/9 (pSMAD1/5/9), was increased by exogenous BMP2 but blocked by DMH1. Based on immunohistochemical and scRNA-seq analyses, upregulation of BMP signaling and ID1/ID3 also occurs in murine models of pre-neoplastic lesions (KC mice) and pancreatitis induced by the cholecystokinin analog caerulein. Moreover, we demonstrate that BMP dependent ID1/ID3 expression occurs in a non-transformed human ductal cell line. Strikingly, even short term caerulein treatment promoted BMP signaling and ID1/ID3 expression in a rat exocrine cell line, consistent with a direct link between inflammation of the exocrine pancreas and BMP/ID signaling. Together, the data suggest that BMP signaling through pSMAD1/5/9 to ID1 and ID3 occurs early in pancreas pathogenesis and that pancreatic cancer cells remain addicted to this important signaling circuit. Future exploration of druggable targets within this pathway could be of therapeutic benefit in the treatment of pancreatitis and PDAC.

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Targeting SDCBP2 in acute myeloid leukemia

Du,

Li,

Chen

et al. 2023

Cellular Signalling

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Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47

Cited by 3 publications

References 37 publications

Assessment of lncRNA biomarkers based on NETs for prognosis and therapeutic response in ovarian cancer

Assessment of lncRNA biomarkers based on NETs for prognosis and therapeutic response in ovarian cancer

Bone Morphogenetic Protein (BMP) signaling upregulates expression of ID1 and ID3 in pancreatitis and pancreatic ductal adenocarcinoma

Targeting SDCBP2 in acute myeloid leukemia

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