Profiling of a novel circadian clock-related prognostic signature and its role in immune function and response to molecular targeted therapy in pancreatic cancer

Jin, Yu; Gong, Shangqing; Shang, Guochen; Hu, Lilin; Li, Gangping

doi:10.18632/aging.204462

Cited by 4 publications

(5 citation statements)

References 42 publications

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“…IL-27 signaling in Tregs plays a crucial role for the proteinogenic properties of Tregs by upregulating CD39 [ 36 ]. Dabrafenib and Linsitinib have been tentatively applied to pancreatic ductal adenocarcinoma with poor prognosis after conventional cytotoxic chemotherapy [ 37 , 38 ]. We found DE-ILRGs related drugs like Dabrafenib and Linsitinib from the CellMiner database, which can provide a new chance for treatment of acute pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

IL27 and IL1RN are causally associated with acute pancreatitis: a Mendelian randomization study

Jing,

Liu,

et al. 2024

Aging

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Background: The interleukin (IL) plays a role in the development of acute pancreatitis (AP). However, the specific IL in AP has not been fully revealed. Therefore, the association between prospective IL and AP was studied via Mendelian randomization (MR). Methods: The HUGO Gene nomenclature committee (HGNC) database provided 47 interleukin related genes (ILRGs). ILRGs and differentially expressed genes (DEGs) from GSE194331 were overlapped to create differently expressed ILRGs (DE-ILRGs). The integrative epidemiology unit (IEU) open genome-wide association study (GWAS) database provided exposure and outcome datasets. Univariate MR (UVMR) analysis using MR-Egger, IVW, simple mode, and weighted mode was done. UVMR results were verified using sensitivity analysis. Drug prediction, MVMR analysis, and PPI network development were also performed. Results: Six DE-ILRGs were obtained. IL27 and IL1RN were substantially causally linked with AP by UVMR analysis (OR = 0.926, P < 0.001 and OR = 1.031, P = 0.023). Our sensitivity analysis showed the dependability of our results. Direct effect of IL27 was suggested by MVMR analysis. In the cytokine receptor binding pathway, IL27 and IL1RN interacted with IL36G and IL1R2. TAE-684, ARQ-680, and 12 other IL1RN and 14 IL27 medications were predicted. Conclusions: IL1RN was identified as a risk factor for acute pancreatitis (AP), but IL27 was found to be a protective factor for AP.

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Section: Discussionmentioning

confidence: 99%

IL27 and IL1RN are causally associated with acute pancreatitis: a Mendelian randomization study

Jing,

Liu,

et al. 2024

Aging

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“…The stress-induced protein kinase CK1 delta (CSNK1D) lies in the long arm of chromosome 17 (17q25.3) in humans, encoding CK1δ, a member of the CK1 family ( Graves et al, 1993 ). Increasing studies have demonstrated that the dysregulation and activity of CK1δ expression are not only found in various cancers but also in different neurological diseases including AD ( Zhu et al, 2022 ; Jin et al, 2023 ). Hence CSNK1D is expected to be a promising treatment target for AD.…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease

Nie,

Duan,

Xie

et al. 2023

Front. Aging Neurosci.

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ObjectivesThis study aimed to make a systematic analysis of cuproptosis-related genes (CRGs) in immunological characterization and predictive drugs in Alzheimer’s disease (AD) through bioinformatics and biological experiments.MethodsThe molecular clusters related to CRGs and associated immune cell infiltrations in AD were investigated. The diagnostic models were constructed for AD and different AD subtypes. Moreover, drug prediction and molecular docking were also performed. Subsequently, a molecular dynamics (MD) simulation was conducted to further verify the findings. Finally, RT-qPCR validation was performed.ResultsThe characterization of 12 AD-related CRGs was evaluated in AD, and a diagnostic model for AD showed a satisfying discrimination power based on five CRGs by LASSO regression analysis. The dysregulated CRGs and activated immune responses partially differed between patients with AD and healthy subjects. Furthermore, two molecular subtypes (clusters A and B) with different immune infiltration characteristics in AD were identified. Similarly, a diagnostic model for different AD subtypes was built with nine CRGs, which achieved a good performance. Molecular docking revealed the optimum conformation of CHEMBL261454 and its target gene CSNK1D, which was further validated by MD simulation. The RT-qPCR results were consistent with those of the comprehensive analysis.ConclusionThis study systematically elucidated the complex relationship between cuproptosis and AD, providing novel molecular targets for treatment and diagnosis biomarkers of AD.

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“…A separate gene expression profile analysis stratified PDAC patients based on genetic risk profiles to utilize targeted molecular therapies. KLF10 was one of thirteen genes involved in the low-risk prognostic signature, relatively defined as improved prognosis and increased sensitivity to cancer treatment [192]. The high-risk cohort, devoid of low-risk genes, had lower CD8 T/B cells and a higher neutrophil count associated with PDAC proliferation and metastasis [192].…”

Section: Klfs As Potential Biomarkersmentioning

confidence: 99%

“…KLF10 was one of thirteen genes involved in the low-risk prognostic signature, relatively defined as improved prognosis and increased sensitivity to cancer treatment [192]. The high-risk cohort, devoid of low-risk genes, had lower CD8 T/B cells and a higher neutrophil count associated with PDAC proliferation and metastasis [192]. When high KLF10 expression was combined with chemoradiotherapy (CRT) treatment, patients had significantly better recurrence-free and overall survival times, indicating KLF10 positively influenced the benefits of adjuvant CRT [193].…”

Section: Klfs As Potential Biomarkersmentioning

confidence: 99%

The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology

Giarrizzo

LaComb

Bialkowska

2023

IJMS

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Krüppel-like factors (KLFs) belong to the family of transcription factors with three highly conserved zinc finger domains in the C-terminus. They regulate homeostasis, development, and disease progression in many tissues. It has been shown that KLFs play an essential role in the endocrine and exocrine compartments of the pancreas. They are necessary to maintain glucose homeostasis and have been implicated in the development of diabetes. Furthermore, they can be a vital tool in enabling pancreas regeneration and disease modeling. Finally, the KLF family contains proteins that act as tumor suppressors and oncogenes. A subset of members has a biphasic function, being upregulated in the early stages of oncogenesis and stimulating its progression and downregulated in the late stages to allow for tumor dissemination. Here, we describe KLFs’ function in pancreatic physiology and pathophysiology.

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Profiling of a novel circadian clock-related prognostic signature and its role in immune function and response to molecular targeted therapy in pancreatic cancer

Cited by 4 publications

References 42 publications

IL27 and IL1RN are causally associated with acute pancreatitis: a Mendelian randomization study

IL27 and IL1RN are causally associated with acute pancreatitis: a Mendelian randomization study

Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease

The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology

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