Variations in Genes Involved in Dormancy Associated with Outcome in Patients with Resected Colorectal Liver Metastases

Overview

Journal Ann Oncol

Publisher Elsevier

Specialty Oncology

Date 2015 May 10

PMID 25957329

Citations 4

Authors

S Stremitzer

W Zhang

D Yang

Y Ning

S Stintzing

Y Sunakawa

A Sebio

S Yamauchi

S Matsusaka

A Parekh

A Barzi

R El-Khoueiry

J Stift

F Wrba

T Gruenberger

H-J Lenz

Affiliations

Soon will be listed here.

Abstract

Background: Tumor dormancy has been described as a state of hibernation. Dormancy can be switched to proliferation by different pathways, which may play a critical role in tumor recurrence. In this study, we investigated genetic variations within genes involved in tumor dormancy and their association with recurrence and outcome in patients with colorectal liver metastases (CLM) who underwent neoadjuvant bevacizumab-based chemotherapy.

Patients And Methods: Genomic DNA was extracted from resected CLM (FFPE) from 149 patients. Single-nucleotide polymorphisms (SNPs) in 14 genes associated with dormancy were analyzed by direct Sanger DNA sequencing and evaluated for response, recurrence-free survival (RFS), overall survival (OS) and recurrence patterns.

Results: NME1 rs34214448 C>A was significantly associated with RFS in univariable analysis (P = 0.039) and with intrahepatic recurrence (P = 0.014). NOTCH3 rs1044009 T>C and CD44 rs8193 C>T showed a significant difference in 3-year OS rates (P = 0.004 and P = 0.042, respectively). With respect to radiological response, CD44 rs8193 C>T variant genotypes were associated with a significantly higher response rate (P = 0.033). Recursive partitioning analyses revealed that Dll4 rs12441495 C>G, NME1 rs34214448 C>A and NOTCH3 rs1044009 T>C were the dominant SNPs predicting histological response, RFS and OS, respectively.

Conclusion: Our data suggest that gene variations within genes involved in tumor dormancy pathways are associated with response and outcome in patients with resected CLM. These data may lead to new and more effective treatment strategies targeting tumor dormancy.

Citing Articles

NME1 and DCC variants are associated with susceptibility and tumor characteristics in Mexican patients with colorectal cancer.

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PMID: 38556604 DOI: 10.1186/s43046-024-00213-7.

Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities.

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Mutant Allele of CD44 (rs8193C>T) and Pum2 Regulatory Element as A Prognosis Factor of Prostate Neoplasms: A Case-Control and In Silico Studies.

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FBX8 promotes metastatic dormancy of colorectal cancer in liver.

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