Dysregulated Cholinergic Network As a Novel Biomarker of Poor Prognostic in Patients with Head and Neck Squamous Cell Carcinoma

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2015 May 10

PMID 25956553

Citations 9

Authors

Ana Cristina Castillo-Gonzalez

Susana Nieto-Ceron

Juan Pablo Pelegrin-Hernandez

Maria Fernanda Montenegro

Jose Antonio Noguera

Maria Fuensanta Lopez-Moreno

Jose Neptuno Rodriguez-Lopez

Cecilio J Vidal

Diego Hellin-Meseguer

Juan Cabezas-Herrera

Affiliations

Soon will be listed here.

Abstract

Background: In airways, a proliferative effect is played directly by cholinergic agonists through nicotinic and muscarinic receptors activation. How tumors respond to aberrantly activated cholinergic signalling is a key question in smoking-related cancer. This research was addressed to explore a possible link of cholinergic signalling changes with cancer biology.

Methods: Fifty-seven paired pieces of head and neck squamous cell carcinoma (HNSCC) and adjacent non-cancerous tissue (ANCT) were compared for their mRNA levels for ACh-related proteins and ACh-hydrolyzing activity.

Results: The measurement in ANCT of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (5.416 ± 0.501 mU/mg protein and 6.350 ± 0.599 mU/mg protein, respectively) demonstrated that upper respiratory tract is capable of controlling the availability of ACh. In HNSCC, AChE and BChE activities dropped to 3.584 ± 0.599 mU/mg protein (p = 0.002) and 3.965 ± 0.423 mU/mg protein (p < 0.001). Moreover, tumours with low AChE activity and high BChE activity were associated with shorter patient overall survival. ANCT and HNSCC differed in mRNA levels for AChE-T, α3, α5, α9 and β2 for nAChR subunits. Tobacco exposure had a great impact on the expression of both AChE-H and AChE-T mRNAs. Unaffected and cancerous pieces contained principal AChE dimers and BChE tetramers. The lack of nerve-born PRiMA-linked AChE agreed with pathological findings on nerve terminal remodelling and loss in HNSCC.

Conclusions: Our results suggest that the low AChE activity in HNSCC can be used to predict survival in patients with head and neck cancer. So, the ChE activity level can be used as a reliable prognostic marker.

Citing Articles

Understanding the role of nerves in head and neck cancers - a review.

Rutkowski K, Gola M, Godlewski J, Starzynska A, Marvaso G, Mastroleo F Oncol Rev. 2025; 18:1514004.

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Preliminary exploration of the expression of acetylcholinesterase in normal human T lymphocytes and leukemic Jurkat T cells.

Gomez-Olivares J, Lopez-Duran R, Enriquez-Flores S, Lopez-Velazquez G, de la Mora-de la Mora I, Garcia-Torres I Biomed Rep. 2024; 21(5):158.

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Changes in the Acetylcholinesterase Enzymatic Activity in Tumor Development and Progression.

Perez-Aguilar B, Marquardt J, Munoz-Delgado E, Lopez-Duran R, Gutierrez-Ruiz M, Gomez-Quiroz L Cancers (Basel). 2023; 15(18).

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A new marker constructed from immune-related lncRNA pairs can be used to predict clinical treatment effects and prognosis: in-depth exploration of underlying mechanisms in HNSCC.

Fan X, Huang Y, Zhong Y, Yan Y, Li J, Fan Y World J Surg Oncol. 2023; 21(1):250.

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Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition.

Li S, Zhao J, Huang R, Travers J, Klumpp-Thomas C, Yu W Environ Health Perspect. 2021; 129(4):47008.

PMID: 33844597 PMC: 8041433. DOI: 10.1289/EHP6993.

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