title: Dysregulated cholinergic network as a novel biomarker of poor prognostic in patients with head and neck squamous cell carcinoma.
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.
authors.affiliation: Molecular Therapy and Biomarkers Research Group, Clinical Analysis Service, University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, Murcia, 30120, Spain. anacristina21_84@hotmail.com.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Castillo-González
authors.affiliation: Molecular Therapy and Biomarkers Research Group, Clinical Analysis Service, University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, Murcia, 30120, Spain. susana.nieto@carm.es.
authors.forename: Susana
authors.initials: S
authors.lastname: Nieto-Cerón
authors.affiliation: Otorhinolaryngology Surgical Service, University Hospital Virgen de la Arrixaca IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, Murcia, 30120, Spain. jppelegrin@gmail.com.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Pelegrín-Hernández
authors.affiliation: Department of Biochemistry and Molecular Biology A, School of Biology, Regional Campus of International Excellence "Campus Mare Nostrum", IMIB-University of Murcia, Murcia, 30100, Spain. ferni1810@gmail.com.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Montenegro
authors.affiliation: Molecular Therapy and Biomarkers Research Group, Clinical Analysis Service, University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, Murcia, 30120, Spain. josea.noguera2@carm.es.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Noguera
authors.affiliation: Molecular Therapy and Biomarkers Research Group, Clinical Analysis Service, University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, Murcia, 30120, Spain. jcabezas@um.es.
authors.forename: María Fuensanta
authors.initials: MF
authors.lastname: López-Moreno
authors.affiliation: Department of Biochemistry and Molecular Biology A, School of Biology, Regional Campus of International Excellence "Campus Mare Nostrum", IMIB-University of Murcia, Murcia, 30100, Spain. neptuno@um.es.
authors.forename: José Neptuno
authors.initials: JN
authors.lastname: Rodríguez-López
authors.affiliation: Department of Biochemistry and Molecular Biology A, School of Biology, Regional Campus of International Excellence "Campus Mare Nostrum", IMIB-University of Murcia, Murcia, 30100, Spain. cevidal@um.es.
authors.forename: Cecilio J
authors.initials: CJ
authors.lastname: Vidal
authors.affiliation: Otorhinolaryngology Surgical Service, University Hospital Virgen de la Arrixaca IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, Murcia, 30120, Spain. diego.hellin@um.es.
authors.forename: Diego
authors.initials: D
authors.lastname: Hellín-Meseguer
authors.affiliation: Molecular Therapy and Biomarkers Research Group, Clinical Analysis Service, University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Ctra Madrid-Cartagena s/n, El Palmar, Murcia, 30120, Spain. juan.cabezas@carm.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Cabezas-Herrera
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D020545:Respiratory Mucosa / Q000201:enzymology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase