Silenced ZNF154 Is Associated with Longer Survival in Resectable Pancreatic Cancer.

Felix Wiesmueller,Janine Roy,Robert Grützmann,Andreas Dahl,Daniela Aust,Christian Pilarsky,Josephin Kopke

doi:10.3390/ijms20215437

Abstract

Pancreatic cancer has become the third leading cause of cancer-related death in the Western world despite advances in therapy of other cancerous lesions. Late diagnosis due to a lack of symptoms during early disease allows metastatic spread of the tumor. Most patients are considered incurable because of metastasized disease. On a cellular level, pancreatic cancer proves to be rather resistant to chemotherapy. Hence, early detection and new therapeutic targets might improve outcomes. The detection of DNA promoter hypermethylation has been described as a method to identify putative genes of interest in cancer entities. These genes might serve as either biomarkers or might lead to a better understanding of the molecular mechanisms involved. We checked tumor specimens from 80 patients who had undergone pancreatic resection for promoter hypermethylation of the zinc finger protein ZNF154. Then, we further characterized the effects of ZNF154 on cell viability and gene expression by in vitro experiments. We found a significant association between ZNF154 hypermethylation and better survival in patients with resectable pancreatic cancer. Moreover, we suspect that the cell growth suppressor SLFN5 might be linked to a silenced ZNF154 in pancreatic cancer.

Highlights

Pancreatic cancer remains one of the deadliest cancer types with an estimated median 5-year survival rate of only 3% [1]
Other types of pancreatic cancer include forms that arise from the exocrine part as well, e.g., acinar cell carcinoma, or tumors that emerge from different parts, e.g., neuroendocrine tumors
After analysis using the log rank test, we found that there was a significant correlation between the status of ZNF154 promoter hypermethylation and postoperative survival: methylation-specific PCR (MSP)-positive patients had a markedly increased postoperative survival, with a median of 652 days, versus MSP-negative patients, who had a median postoperative survival of 392 days

Summary

Introduction

Pancreatic cancer remains one of the deadliest cancer types with an estimated median 5-year survival rate of only 3% [1]. More than 90% of pancreatic cancers are diagnosed in patients 55 years of age or older [2] and the incidence is projected to rise in the future [3]. The term pancreatic cancer usually refers to pancreatic ductal adenocarcinoma (PDAC). Other types of pancreatic cancer include forms that arise from the exocrine part as well, e.g., acinar cell carcinoma, or tumors that emerge from different parts, e.g., neuroendocrine tumors. Symptoms are sparsely found in patients with early disease. Unspecific findings, such as weight loss or abdominal pain, make this entity hard to diagnose [5]

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