Prognostic Value of COX-2, NF-κB, and Sp1 Tissue Expressions in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

Renaldi, Kaka; Simadibrata, Marcellus; Rahadiani, Nur; Handjari, Diah Rini; William, Andy; Sinuraya, Fira Alyssa Gabriella; Makmun, Dadang

doi:10.5152/tjg.2021.211106

Cited by 3 publications

(5 citation statements)

References 40 publications

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“…Jiang et al showed that Sp1 expression was associated with a higher tumor grade, a higher rate of lymph node metastasis, and a shorter OS [ 29 ]. Overall, our meta−analysis of previous studies showed that Sp1 expression is an independent predictor of a worse prognosis in PDAC patients (aHR = 3.47; 95% CI 1.52–7.94) [ 24 ]. We also found that the co−expression of all four proteins (nuclear NF−κB +/COX−2 +/Sp1 +/c−Jun +) was associated with a longer OS than that in other patient groups, although this was statistically insignificant.…”

Section: Discussionmentioning

confidence: 86%

“…This association holds when controlling for other variables ( p = 0.02) [ 28 ]. Overall, the pooled results of these two studies from our meta−analysis showed that patients with a positive NF−κB expression had a worse OS than those without it, but this was not significant when controlling for other variables (aHR = 2.38; 95% CI 0.68–8.25) [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Our previously published meta−analysis showed that, overall, PDAC patients with a positive COX−2 expression had trends of a lower OS than those with negative expressions. However, that association was insignificant when the other clinicopathological variables were controlled (aHR = 1.30; 95% CI 0.80–2.13) [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…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 ]. However, a more recent meta−analysis that was published by our group showed that this association was not significant when controlling for other variables [ 24 ]. Compared to those on COX−2, few studies have investigated the effects of the NF−κB, Sp1, and c−Jun expressions on PDAC patient survival [ 14 , 16 , 18 ].…”

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: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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“…Various cytokines, chemokines and growth factors are detected at elevated levels in pancreatic cancer cells. The elevation in expression is often mediated by mutations in KRAS , epithelial growth factor receptor ( EGFR ), phosphatidylinositol 3-kinase (PI3K, PIK3CA ) and TP53 [ 69 ]. These mutations can contribute to elevated levels of the NF-κB signaling which regulates expression of many inflammatory cytokines, including IL-6, IL-8 and IL-18 [ 70 ].…”

Section: Altered Expression Of Growth Factors Their Receptors and Dow...mentioning

confidence: 99%

Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression

McCubrey

Yang

Abrams

et al. 2022

Cells

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Approximately 90% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is the fourth leading cause of cancer death world-wide. Therapies for PDAC are largely ineffective due to the dense desmoplastic tumor microenvironment which prevents chemotherapeutic drugs and small molecule inhibitors from exerting effective anti-cancer effects. In this review, we will discuss the roles of TP53 and miRs on the PDAC tumor microenvironment and how loss of the normal functions of TP53 promote tumor progression. The TP53 gene is mutated in approximately 50% of pancreatic cancers. Often, these TP53 mutations are point mutations which confer additional functions for the TP53 proteins. These are called gain of function (GOF) mutations (mut). Another class of TP53 mutations are deletions which result in loss of the TP53 protein; these are referred to TP53-null mutations. We have organized this review into various components/properties of the PDAC microenvironment and how they may be altered in the presence of mutant TP53 and loss of certain miR expression.

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Pharmacoinformatic screening of phytoconstituent and evaluation of its anti-PDAC effect using in vitro studies

Gupta

Banavath

Tejavath

2022

Journal of Biomolecular Structure and Dynamics

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Prognostic Value of COX-2, NF-κB, and Sp1 Tissue Expressions in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

Cited by 3 publications

References 40 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

Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression

Pharmacoinformatic screening of phytoconstituent and evaluation of its anti-PDAC effect using in vitro studies

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