Transcriptome data‐based status of PI3K/AKT/mTOR pathway indicates heterogeneity and immune modulation in patients with pancreatic ductal adenocarcinoma

Xie, Peng; Tan, Shina; Li, Haifeng; Tang, Haodong; Zhou, Jiahua

doi:10.1002/jgm.3570

Cited by 3 publications

References 38 publications

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NF-κB Mediated Disruption of Pancreatic Signaling Pathways and its Implications for the Risk of Pancreatic Adenocarcinoma: a systematic review

Shafi,

Rajpar,

Aakash

et al. 2024

Preprint

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ObjectiveThe objective of this study is to determine how NF-κB-mediated inflammation disrupts pancreatic signaling pathways and the resultant increase in the risk of Pancreatic Adenocarcinoma.BackgroundPancreatic adenocarcinoma’s severity and poor prognosis underscore the critical role of NF-κB-mediated inflammation in disease progression. NF-κB activation disrupts key pancreatic signaling pathways by promoting cell proliferation, inhibiting differentiation, and facilitating oncogenic transformation. Understanding these mechanisms is essential for developing targeted therapies that mitigate NF-κB-induced damage, improve early detection through biomarkers, and enhance treatment outcomes for pancreatic cancer patients.MethodsDatabases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to investigate how NF-κB-mediated inflammation disrupts pancreatic signaling pathways and the resultant increase in the risk of Pancreatic Adenocarcinoma. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate the research question. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).ResultsNF-κB-mediated inflammation significantly disrupts several critical pancreatic signaling pathways, leading to oncogenic transformations and increased risk of pancreatic adenocarcinoma. Specifically, NF-κB activation alters Notch signaling, causing abnormal cell differentiation; disrupts Wnt and Shh pathways, enhancing cellular proliferation; and perturbs FGF and TGF-β pathways, leading to impaired cellular homeostasis. Additionally, NF-κB interferes with BMP signaling, contributing to dysregulated cell growth; modulates the PI3K/Akt/mTOR pathway, promoting cell survival and tumor growth; affects JAK/STAT signaling, resulting in enhanced inflammatory responses and tumor progression; and disrupts Hippo pathway components, which normally regulate organ size and inhibit tumorigenesis.ConclusionNF-κB-mediated inflammation disrupts critical pancreas signaling pathways—Notch, Wnt, Hippo, JAK/STAT, and others—promoting cell survival, proliferation, and oncogenic transformation. This dysregulation, seen in chronic inflammation, elevates pancreatic adenocarcinoma risk by fostering a tumorigenic microenvironment. These interactions highlight NF-κB as a central player in pancreatic cancer pathogenesis. Targeting NF-κB and associated pathways emerges as crucial for therapeutic strategies aimed at mitigating inflammatory damage and improving outcomes in pancreatic adenocarcinoma treatment.

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NF-κB Mediated Disruption of Pancreatic Signaling Pathways and its Implications for the Risk of Pancreatic Adenocarcinoma: a systematic review

Shafi,

Rajpar,

Aakash

et al. 2024

Preprint

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Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?

Ouissam,

Hind,

Sami Aziz

et al. 2024

Ther Adv Med Oncol

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Pancreatic cancer (PC) is an aggressive disease that is challenging to treat and is associated with a high mortality rate. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), and the existing treatment options are insufficient for PDAC patients. Due to the complexity and heterogeneity of PDAC, personalized medicine is necessary for effectively treating this illness. To achieve this, it is essential to understand the mechanism of PDAC carcinogenesis. Targeted therapies are a promising strategy to improve patient outcomes. Aberrant activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a crucial role in PC pathogenesis, from initiation to progression. This review provides a comprehensive overview of the current state of knowledge regarding the PI3K pathway in PDAC, summarizes clinical data on PI3K pathway inhibition in PDAC, and explores potential effective combinations that are a promising direction requiring further investigation in PDAC.

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Machine Learning-Based Disulfidptosis-Related lncRNA Signature Predicts Prognosis, Immune Infiltration and Drug Sensitivity in Hepatocellular Carcinoma

Pu,

Sun,

et al. 2023

Preprint

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Disulfidptosis plays a crucial role in the development and progression of Hepatocellular Carcinoma (HCC). However, the significance of disulfidptosis-related Long non-coding RNAs (DRLs) in the prognosis and immunotherapy of HCC remains unclear. Based on The Cancer Genome Atlas (TCGA) database, we used Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression model to construct DRL Prognostic Signature (DRLPS)-based risk scores. Survival analysis was then performed and a nomogram was constructed. Moreover, we performed functional enrichment annotation, immune infiltration analyses and drug sensitivity analyses. Five DRLs, including AL590705.3, AC072054.1, AC069307.1, AC107959.3 and ZNF232-AS1, were identified to construct prognostic signature. DRLPS-based risk scores exhibited a better predictive efficacy of survival than conventional clinical features. The nomogram showed a high degree of congruence between the predicted survival and observed survival. Gene set were mainly enriched in cell proliferation, differentiation and growth function related pathways. Immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. Additionally, the high-risk group exhibited higher sensitivity to Afatinib, Fulvestrant, Gefitinib, Osimertinib, Sapitinib, and Taselisib. In conclusion, our study highlighted the potential utility of the constructed DRLPS in the prognosis prediction of HCC patients, which demonstrated promising clinical application value.

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Transcriptome data‐based status of PI3K/AKT/mTOR pathway indicates heterogeneity and immune modulation in patients with pancreatic ductal adenocarcinoma

Cited by 3 publications

References 38 publications

NF-κB Mediated Disruption of Pancreatic Signaling Pathways and its Implications for the Risk of Pancreatic Adenocarcinoma: a systematic review

NF-κB Mediated Disruption of Pancreatic Signaling Pathways and its Implications for the Risk of Pancreatic Adenocarcinoma: a systematic review

Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?

Machine Learning-Based Disulfidptosis-Related lncRNA Signature Predicts Prognosis, Immune Infiltration and Drug Sensitivity in Hepatocellular Carcinoma

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