title: Possible prognostic value of BORIS transcript variants ratio in laryngeal squamous cell carcinomas - a pilot study.
abstract: BORIS is a paralog of a highly conserved, multi-functional chromatin factor CTCF. Unlike CTCF, which has been shown to possess tumor-suppressive properties, BORIS belongs to the "cancer/testis antigen" family normally expressed only in germ cells and aberrantly activated in a variety of tumors. The consequences of BORIS expression, relative abundance of its isoforms, and its role in carcinogenesis have not been completely elucidated. It activates transcription of hTERT and MYC, genes relevant for laryngeal carcinoma progression. In this study, BORIS expression has been analyzed at the transcriptional level by RT-PCR and protein level by semi-quantitative immunohistochemistry in 32 laryngeal squamous cell carcinomas and adjacent non-tumorous tissue. BORIS was detected in 44 % (14/32) laryngeal squamous cell carcinoma samples, while it was detected only in one normal, tumor-adjacent tissue sample. Tree based survival analysis, using the recursive partitioning algorithm mvpart, extracted the ratio of relative abundance of BORIS transcript variants containing exon 7 (BORIS 7+) and those lacking exon 7 (BORIS 7-) as an independent prognostic factor associated with disease relapse during a 5-year follow-up period. Patients having BORIS 7+/BORIS 7- ratio ≥1 had a higher rate of disease relapse than patients with BORIS 7+/BORIS 7- ratio <1. Hazard ratio for that group, based on Cox Proportional Hazard Regression, was 3.53. This is the first study analyzing expression of BORIS protein and transcript variants in laryngeal squamous cell carcinoma relative to its possible prognostic value for recurrence and overall survival.
authors.affiliation: Laboratory for Epigenomics, Ruđer Bošković Institute, Bijenička cesta 54, 10002, Zagreb, Croatia, rnovak@irb.hr.
authors.forename: Renata
authors.initials: R
authors.lastname: Novak Kujundžić
authors.forename: Ivana
authors.initials: I
authors.lastname: Grbeša
authors.forename: Mirko
authors.initials: M
authors.lastname: Ivkić
authors.forename: Božo
authors.initials: B
authors.lastname: Krušlin
authors.forename: Paško
authors.initials: P
authors.lastname: Konjevoda
authors.forename: Koraljka
authors.initials: K
authors.lastname: Gall Trošelj
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D007830:Larynx / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger