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

Author:

Renaldi Kaka123ORCID,Simadibrata Marcellus23,Rahadiani Nur4ORCID,Handjari Diah Rini4,Harahap Alida Roswita1,Harimurti Kuntjoro3,Zubir Nasrul5,Siregar Lianda6,Loho Imelda Maria6,Suzanna Evlina7,Prawirodihardjo Bonita8,Hidajat Heriawaty9,Widodo Budi10,Rahniayu Alphania11ORCID,Tambun Renaningtyas12,William Andy3ORCID,Makmun Dadang23

Affiliation:

1. Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia

2. Division of Gastroenterology, Pancreatobiliary and Gastrointestinal Endoscopy, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia

3. Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia

4. Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia

5. Division of Gastroenterology, Department of Internal Medicine, Dr. M. Djamil Hospital, Padang 25171, Indonesia

6. Division of Gastroenterohepatology, Dharmais National Cancer Hospital, Jakarta 11420, Indonesia

7. Department of Anatomical Pathology, Dharmais National Cancer Hospital, Jakarta 11420, Indonesia

8. Department of Anatomical Pathology, Fatmawati Central General Hospital, Jakarta 12430, Indonesia

9. Department of Anatomical Pathology, Persahabatan Central General Hospital, Jakarta 13230, Indonesia

10. Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga−Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia

11. Department of Anatomical Pathology, Faculty of Medicine, Universitas Airlangga−Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia

12. Department of Anatomical Pathology, St. Carolus Hospital, Jakarta 10440, Indonesia

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.

Funder

Directorate of Research and Development, Universitas Indonesia, under Hibah PUTI 2022

Publisher

MDPI AG

Subject

General Medicine

Reference51 articles.

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