title: COL1A1, PRPF40A, and UCP2 correlate with hypoxia markers in non-small cell lung cancer.
abstract: OBJECTIVE
  Collagen 1A1 (COL1A1), RNA-binding and pre-mRNA Processing Factor (PRPF40A), and Uncoupling Protein 2 (UCP2) were identified as downstream effectors of cytoglobin (CYGB), which was shown implicated in tumour biology. Although these three genes have been previously associated with cancer, little is known about their status in lung malignancies.
  
  
  METHODS
  Hereby, we investigated the expression and promoter methylation of COL1A1, PRPF40A, and UCP2 in 156 non-small cell lung cancer (NSCLC) and adjacent normal tissues.
  
  
  RESULTS
  We demonstrate that COL1A1 and PRPF40A mRNAs are significantly overexpressed in NSCLC (p < 1 × 10-4), while UCP2 exhibits a trend of upregulation (p = 0.066). Only COL1A1 promoter revealed hypermethylation in NSCLCs (36%), which was particularly evident in squamous cell carcinomas (p = 0.024) and in the tumours with moderate-to-good differentiation (p = 0.01). Transcript level of COL1A1, as well as PRPF40A and UCP2, exhibited striking association (p ≤ 0.001) with the expression of hypoxia markers. In addition, we demonstrate in lung cancer cell lines exposed to hypoxia or oxidative stress that COL1A1 transcription significantly responds to oxygen depletion, while other genes showed the modest upregulation in stress conditions.
  
  
  CONCLUSIONS
  In conclusion, our data revealed that COL1A1, UCP2, and PRPF40A are novel players implicated in the complex network of hypoxia response in NSCLC.
authors.affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Rd, Liverpool, L3 9TA, UK. u.oleksiewicz@gmail.com.|Department of Cancer Immunology, Poznan University of Medical Sciences, 15 Garbary, 61-866, Poznan, Poland. u.oleksiewicz@gmail.com.
authors.forename: Urszula
authors.identifier: http://orcid.org/0000-0003-0357-9284
authors.initials: U
authors.lastname: Oleksiewicz
authors.affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Rd, Liverpool, L3 9TA, UK.
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Liloglou
authors.affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Rd, Liverpool, L3 9TA, UK.|Department of Surgery, General Hospital of Didymoteicho, 152 25th Maiou street, 68300, Didymoteicho, Greece.
authors.forename: Kalliopi-Maria
authors.initials: KM
authors.lastname: Tasopoulou
authors.affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Rd, Liverpool, L3 9TA, UK.|Faculty of Health and Medical Sciences, University of Surrey, AY Building, Guildford, Surrey, GU2 7 XH, UK.
authors.forename: Nikoleta
authors.initials: N
authors.lastname: Daskoulidou
authors.affiliation: Department of Pathology, University of Liverpool, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Gosney
authors.affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Rd, Liverpool, L3 9TA, UK.
authors.forename: John K
authors.initials: JK
authors.lastname: Field
authors.affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Rd, Liverpool, L3 9TA, UK. georgexinarianos@hotmail.com.
authors.forename: George
authors.initials: G
authors.lastname: Xinarianos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D015687:Cell Hypoxia / Q000502:physiology; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D059467:Transcriptome; D000071246:Uncoupling Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C491404:PRPF40A protein, human; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2
keywords: COL1A1; Hypoxia; Non-small cell lung cancer; PRPF40A; UCP2