Weighted gene co-expression network analysis reveals key stromal prognostic markers in pancreatic cancer DOI Creative Commons

Giovanna Mantini,

Antonio De Agostini,

M. Tufo

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 30, 2024

In recent years, it has been shown that stroma compartment can favor tumor proliferation and aggressiveness. Although extensive research with network analyses such as Weighted Gene Co-expression Network Analysis (WGCNA) conducted on pancreatic cancer its stromal components, WGCNA not previously applied to isolate identify genes associated the abundance of survival outcome from bulk RNA data. We investigated gene expression profile clinical information 140 ductal adenocarcinoma patients TCGA. analysis was performed using four modules were found be patients' traits. Specifically, one module 2459 genes, sample content. Subsequently, those further analyzed for association through log-rank test Cox regression. HPGDS ITGA9-AS1 emerged significant indicators favorable prognosis while KCMF1 YARS1 implicated in poorer prognostic outcomes. Importantly, stromal-specific TMA cohort Human Protein Atlas. Single GSEA showed is enriched signature Moffitt Puleo. These findings suggest we uncovered a specific putative markers.

Language: Английский

The extracellular matrix drives guanylate production and protects pancreatic cancer cells from oxaliplatin-induced DNA damage. DOI Creative Commons
Georgios Efthymiou,

Coralie Compare,

Eugénie Lohmann

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract The excessive production of extracellular matrix (ECM) and the metabolic adaptations in pancreatic ductal adenocarcinoma (PDAC) contribute individually to enhanced chemoresistance, dramatic tumor progression dismal patient survival. However, ECM-driven alterations that promote chemoresistance PDAC are so far unexplored. Here, we use in-vitro -generated ECM bio-scaffolds recapitulate cell-ECM interactions induce broad cells. High-throughput integration multi-omics datasets coupled with tracing showed enhances generation guanylates cells, accumulation which alleviates oxaliplatin-induced DNA damage, boosts cell proliferation. These events guided by guanosine monophosphate (GMP)-producing enzymes Impdh Gmps, expression correlated matrisomal repair genes samples. We propose targeting processes, like activity, may be an effective therapeutic approach for patients bypasses negative side effects direct itself.

Language: Английский

Citations

0
The Cytotoxic Effect of Crocin and Chrysin on the AsPC-1 Pancreatic Cancer Cell Line is Related to Inhibition of Nutrient Uptake DOI Creative Commons
Sara Pinto, Nelson Andrade, Francisca Carmo

et al.

PharmaNutrition, Journal Year: 2025, Volume and Issue: 31, P. 100432 - 100432

Published: Jan. 16, 2025

Language: Английский

Citations

0
Ribosome Biogenesis, Altered Metabolism and Ribotoxic Stress Response in Pancreatic Ductal Adenocarcinoma Tumor Microenvironment DOI
Sanjib Chaudhary, Jawed A. Siddiqui, Ramesh Pothuraju

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217484 - 217484

Published: Jan. 1, 2025

Language: Английский

Citations

0
Isoferulic Acid Inhibits Proliferation and Migration of Pancreatic Cancer Cells, and Promotes the Apoptosis of Pancreatic Cancer Cells in a Mitochondria‐Dependent Manner Through Inhibiting NF‐κB Signalling Pathway DOI Open Access

Suqin Sun,

Rong Fan, Chang Li

et al.

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2025, Volume and Issue: 52(3)

Published: Jan. 24, 2025

ABSTRACT Isoferulic acid (IA), a derivative of cinnamic acid, is derived from Danshen and exhibits anticancer properties by disrupting cancer cell activities. However, its role in pancreatic cancer, the “king cancer”, was unknown. In this study, cells were subjected to treatment with IA (6.25, 12.5, 25 μM), nude mice injected received at doses 7.5 mg/kg/day or 30 oral administration. CCK8, Annexin V‐FITC/propidium iodide (PI) double staining TUNEL assay conducted evaluate viability apoptosis. Hoechst comet employed measure DNA damage. Mitochondrial membrane potential (MMP) analysis carried out explain mitochondrial EdU wound healing performed for proliferation migration detection. Immunofluorescence western blot used explore mechanism. We found that reduced induced apoptosis, as evidenced an increase V‐FITC + PI − populations, brighter staining, more percentage tail DNA. Furthermore, decreased MMP changed levels apoptosis‐related proteins. The inhibited treatment. Mechanically, downregulated phosphorylation IĸBα p65 nuclear translocation, consequently suppressing NF‐κB pathway. general, suppressed migration, caused apoptosis mitochondria‐dependent manner through blocking signalling pathway, indicating may be therapeutic strategy cancer.

Language: Английский

Citations

0
Neurturin-Induced Activation of GFRA2-RET Axis Potentiates Pancreatic Cancer Glycolysis via Phosphorylated Hexokinase 2 DOI
Ran Cui, Gaoming Wang, Fuguo Liu

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217583 - 217583

Published: Feb. 1, 2025

Language: Английский

Citations

0
肿瘤巨胞饮的分子调控机制研究进展 DOI
Chunlan Wang,

Zihang Yuan,

Bo Lin

et al.

Chinese Science Bulletin (Chinese Version), Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Citations

0
The role of metabolic reprogramming in liver cancer and its clinical perspectives DOI Creative Commons
Mengxiao Lu, Yingjie Wu, Min Xia

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Nov. 14, 2024

Primary liver cancer (PLC), which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a leading cause of cancer-related death worldwide. Chronic diseases, such as hepatitis B C infections metabolic dysfunction-associated steatotic disease (MASLD), are key risk factors for PLC. Metabolic reprogramming, defining feature cancer, enables cells to adapt the demands rapid proliferation challenging tumor microenvironment (TME). This manuscript examines pivotal role reprogramming in PLC, with an emphasis on alterations glucose, lipid, amino acid metabolism that drive progression. The Warburg effect, marked by increased glycolysis, facilitates energy production biosynthesis cellular components HCC. Changes lipid metabolism, including elevated de novo fatty synthesis oxidation, support membrane formation storage essential cell survival. Amino particularly glutamine utilization, supplies critical carbon nitrogen nucleotide maintains redox homeostasis. These adaptations not only enhance growth invasion but also reshape TME, promoting immune escape. Targeting these pathways presents promising therapeutic opportunities review underscores interaction between immunity, suggesting potential targets innovative strategies. A comprehensive understanding PLC’s intricate landscape may lead more effective treatments better patient outcomes. Integrating metabolomics, genomics, proteomics future research will be vital identifying precise advancing personalized therapies cancer.

Language: Английский

Citations

3
Pancreatic cancer is feeling the heat DOI Creative Commons
Saumya Maru, Elizabeth M. Jaffee

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(10), P. e010124 - e010124

Published: Oct. 1, 2024

Pancreatic adenocarcinoma (PDAC) is considered an immunologically ‘cold’ tumor that fails to attract or support effector T cells. Most PDACs are resistant immune checkpoint blockade due the complex signaling pathways exist within its microenvironment. Recent advances in genomic and proteomic technology finally uncovering inflammatory cellular intercellular signals require modulation reprogramming. The goal ‘turn up heat’ on with combination immunotherapies incorporate cell activating agents modulatory agents, successfully eradicate tumors. Here, we discuss progress promising new research moving field toward this goal.

Language: Английский

Citations

2
Selective metabolic regulations by p53 mutant variants in pancreatic cancer DOI Creative Commons
Sabrina Caporali, Alessio Butera, Alessia Ruzza

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Nov. 26, 2024

Approximately half of all human cancers harbour mutations in the p53 gene, leading to generation neomorphic mutant proteins. These mutants can exert gain-of-function (GOF) effects, potentially promoting tumour progression. However, clinical significance GOF mutations, as well selectivity individual variants, remains controversial and unclear.

Language: Английский

Citations

2
Unveiling the Promise: Navigating Clinical Trials 1978–2024 for PDAC DOI Open Access
A. Domínguez,

M Perz,

Yi Xu

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(21), P. 3564 - 3564

Published: Oct. 23, 2024

Despite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one the most difficult cancers to diagnose and treat effectively. Although there have been improvements in 5-year overall survival rate, it is still very low at 12.5%. The limited efficacy current therapies, even when PDAC detected early, underscores aggressive nature disease urgent need for more effective treatments. Clinical management relies heavily on a repertoire therapeutic interventions, highlighting significant gap between research efforts available Over 4300 clinical trials or are currently investigating different treatment modalities diagnostic strategies PDAC, including targeted immunotherapies, precision medicine approaches. These aim develop treatments improve early detection methods through advanced imaging techniques blood-based biomarkers. This review seeks categorize analyze PDAC-related across various dimensions understand why so few chemotherapeutic options patients despite numerous being conducted. aims provide comprehensive nuanced understanding landscape trials, with overarching goal identifying opportunities accelerate progress drug development patient outcomes fight against this devastating disease.

Language: Английский

Citations

1