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

NF-κB、COX-2、Sp1、c-Jun在胰腺导管腺癌中的表达及与患者生存的关系

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作者:Kaka Renaldi, Marcellus Simadibrata, Nur Rahadiani, Diah Rini Handjari, Alida Roswita Harahap, Kuntjoro Harimurti, Nasrul Zubir, Lianda Siregar, Imelda Maria Loho, Evlina Suzanna, Bonita Prawirodihardjo, Heriawaty Hidajat, Budi Widodo, Alphania Rahniayu, Renaningtyas Tambun, Andy William, Dadang Mak

Abstract

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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