Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
Division of Gastroenterology and Hepato Billiary Pathology, Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/ Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia.
Turk J Gastroenterol. 2021 Nov;32(11):956-970. doi: 10.5152/tjg.2021.211106.
Pancreatic ductal adenocarcinoma (PDAC) is deadly cancer with a poor prognosis. Molecular prognostic markers are needed to predict the patient's survival. The cyclooxygenase-2 enzyme (COX-2) and its 2 major transcription factors--nuclear factorkappa B (NF-κB) and specificity protein 1 (Sp1)--are activated during inflammation caused by neoplasia. Several studies have investigated the association between the COX-2, NF-κB, and Sp1 tissue expressions with the patient's overall survival. Therefore, we conducted this systematic review and meta-analysis to evaluate those studies.
We searched for relevant articles from the MEDLINE database through June 2020. Studies were eligible if they included dichotomized tissue protein expression status and the overall survival as the outcome. We used RevMan and ProMeta programs to perform the meta-analysis.
We identified 11 eligible studies. The meta-analysis showed that COX-2 tissue expression was associated with decreased overall survival (crude HR = 1.35; 95% CI, 1.05-1.74), although the result was not significant when controlling for other covariates. The NF-κB tissue expression was associated with decreased overall survival (crude HR = 2.18; 95% CI, 1.49-3.18), although it was not significant when controlling for other covariates. The Sp1 tissue expression showed significantly decreased overall survival even when adjusted with other covariates (aHR = 3.47; 95% CI, 1.52-7.94). The limitations included searching only for English publications and the substantial heterogeneity among the studies.
COX-2, NF-κB, and Sp1 tissue expressions have the potential to be used as prognostic markers in PDAC. Further studies are still needed to clarify the associations.
胰腺导管腺癌（PDAC）是一种预后不良的致命癌症。需要分子预后标志物来预测患者的生存情况。环氧化酶-2 酶（COX-2）及其 2 个主要转录因子——核因子κB（NF-κB）和特异性蛋白 1（Sp1）——在肿瘤引起的炎症中被激活。几项研究已经研究了 COX-2、NF-κB 和 Sp1 组织表达与患者总生存之间的关系。因此，我们进行了这项系统评价和荟萃分析来评估这些研究。
我们从 MEDLINE 数据库中搜索了截至 2020 年 6 月的相关文章。如果研究包括组织蛋白表达状态的二分法和作为结局的总生存，则研究是合格的。我们使用 RevMan 和 ProMeta 程序进行荟萃分析。
我们确定了 11 项合格的研究。荟萃分析表明，COX-2 组织表达与总生存降低相关（未调整 HR = 1.35；95%CI，1.05-1.74），尽管在控制其他协变量后结果不显著。NF-κB 组织表达与总生存降低相关（未调整 HR = 2.18；95%CI，1.49-3.18），尽管在控制其他协变量后结果不显著。Sp1 组织表达即使在调整其他协变量后也显示出明显降低的总生存（调整后的 HR = 3.47；95%CI，1.52-7.94）。局限性包括仅搜索英文出版物以及研究之间存在很大的异质性。
COX-2、NF-κB 和 Sp1 组织表达有可能成为 PDAC 的预后标志物。仍需要进一步的研究来阐明这些关联。
