EGFR, but not COX‑2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival

Fagman, Johan Bourghardt; Ljungman, David; Falk, Peter; Iresjö, Britt‐Marie; Engström, Christer; Naredi, Peter; Lundholm, Kent

doi:10.3892/ol.2019.10224

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…Previous studies that have investigated the prognostic significance of COX−2 in PDAC showed inconsistent results. A study by Fagman et al on 32 patients with PDAC showed that COX−2 expression was not independently associated with survival [ 19 ]. Meanwhile, several studies have reported that COX−2 expression was independently associated with a worse OS for PDAC patients [ 20 , 21 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is important that we study these proteins, because their overexpression could potentially represent prognostic factors in cancers. Several studies have investigated the utility of COX−2 expression for predicting the patient survival in PDAC, with conflicting results [ 19 , 20 , 21 , 22 ]. A meta−analysis by Wang et al reported that the PDAC patients who expressed COX−2 had worse survival than those who did not [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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The Expressions of NF−κB, COX−2, Sp1, and c−Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival

et al. 2023

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Chronic inflammation is a crucial driver of carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Several studies have investigated the prognostic significance of cyclooxygenase−2 (COX−2) expression in PDAC patients, obtaining conflicting results. Nuclear factor kappa−B (NF−κB), specificity protein 1 (Sp1), and c−Jun are known as the transcription factors of the COX2 gene. This exploratory observational study investigated the association of the NF−κB, COX−2, Sp1, and c−Jun expressions with patient survival in PDAC. We used the immunohistochemical method to detect the PDAC tissue expressions of NF−κB (RelA/p65), COX−2, Sp1, and c−Jun. The expressions of these proteins were correlated with the overall survival (OS) and other clinicopathological characteristics of PDAC patients. We obtained 53 PDAC specimens from resections and biopsies. There were significant correlations between the four proteins’ expressions in the PDAC tissues. The expression of the cytoplasmic (aHR = 0.31; 95% CI 0.11–0.90; p = 0.032) or nuclear NF−κB (aHR = 0.22; 95% CI 0.07–0.66; p = 0.007) was independently associated with a better prognosis in the PDAC patients. COX−2, Sp1, and c−Jun showed no significant association with a prognosis in the PDAC patients. The PDAC patients who expressed NF−κB had a better prognosis than the other patients, which suggests that the role of inflammation in PDAC is more complex than previously thought.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Expressions of NF−κB, COX−2, Sp1, and c−Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival

et al. 2023

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“…EGFR is a transmembrane protein closely related to multiple pathological processes such as the proliferation, invasion, and metastasis of pancreatic cancer cells. Clinical studies have shown that the overexpression of EGFR could shorten the average overall survival rate of patients after PDAC resection and can be used as an independent predictor [ 39 ]. Accumulating evidence demonstrated that MAPK signaling promotes pathogenesis and biochemical progress of tumor cells [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Study on the Potential Molecular Mechanism of Xihuang Pill in the Treatment of Pancreatic Cancer Based on Network Pharmacology and Bioinformatics

Wang

Zhang

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. We aimed to analyze the possible molecular mechanism of Xihuang pill (XHP) in the treatment of pancreatic cancer based on methods of network pharmacology, molecular docking, and bioinformatics. Methods. The main active components and targets were obtained through the TCMSP database, the BATMAN-TCM database, and the Chemistry database. The active ingredients were screened according to the “Absorption, Distribution, Metabolism, Excretion” (ADME) principle and supplemented with literature. We searched GeneCards, OMIM, TTD, and DrugBank databases for pancreatic cancer targets. The targets of disease and ingredients were intersected to obtain candidate key targets. Then, we constructed a protein-protein interaction (PPI) network for protein interaction analysis and a composition-key target map to obtain essential effective ingredients. Metascape was used to perform functional enrichment analysis to screen critical targets and pathways. The expression and prognosis of key targets were examined and analyzed, and molecular docking was carried out. Results. A total of 52 active ingredients of XHP, 121 candidate targets, and 52 intersecting targets were obtained. The core active ingredients of XHP for the treatment of pancreatic cancer were quercetin, 17-β-estradiol, ursolic acid, and daidzein. The core targets were EGFR, ESR1, MAPK1, MAPK8, MAPK14, TP53, and JUN, which were highly expressed genes of pancreatic cancer. Among them, EGFR and MAPK1 were significantly correlated with the survival of pancreatic cancer patients. The key pathway was the EGFR/MAPK pathway. The molecular docking results indicated that four active compositions had good binding ability to key targets. Conclusion. The molecular mechanism of XHP for the treatment of pancreatic cancer involved multiple components, multiple targets, and multiple pathways. This research theoretically elucidated the ameliorative effect of XHP against pancreatic cancer and might provide new ideas for further research on the treatment of pancreatic cancer.

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“…EGFR is highly expressed in a variety of tumours, and is associated with tumour occurrence and development and poor prognosis [ 74 , 75 ]. It has been reported that EGFR overexpression can be detected in up to 90% of PC tumour tissues, and that overexpressed EGFR is closely involved in the progression of PC and the poor prognosis of PC patients [ 76 , 77 ]. It was also confirmed that EGFR is an effective target for PC prevention and treatment [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation

Huang

Meng

et al. 2021

Chin Med

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Background Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. Methods Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. Results The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. Conclusions Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI.

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EGFR, but not COX‑2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival

Cited by 10 publications

References 38 publications

The Expressions of NF−κB, COX−2, Sp1, and c−Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival

The Expressions of NF−κB, COX−2, Sp1, and c−Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival

Study on the Potential Molecular Mechanism of Xihuang Pill in the Treatment of Pancreatic Cancer Based on Network Pharmacology and Bioinformatics

A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation

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