title: Host gene expression profiling of cervical smear is eligible for cancer risk evaluation.
abstract: OBJECTIVE
  Uterine cervical carcinoma (CC) is known to be a delayed consequence of human papillomavirus (HPV) infection. Considering the reported influence of HPV on host genome activity, we conceived an approach to capture human gene expression profiles corresponding to increased risks of carcinogenesis.
  
  
  METHODS
  A sample set of 143 female participants included a 'control' group of 23, a 'pathology' group of 83 (cervical abnormalities of varied grade including 10 cases of CC), and a 'HPV carrier' group of 37 (infected but manifesting normal cytology). HPV detection, viral load measurements and gene expression profiling were performed by real-time PCR assays.
  
  
  RESULTS
  Gradual increase in expression of proliferation markers and a decrease in expression of proapoptotic genes, some receptors, PTEN and PTGS2 were demonstrated for progressive grades of cervical intraepithelial neoplasia leading to cancer. All reported trends were statistically significant, for instance, correlation of gene expression values for MKI67, CCNB1 and BIRC5. A model was proposed that employed mRNA concentrations for genes MKI67, CDKN2A, PGR and BAX. Prompt distinction between the norm and the cancer, provided by initial calculation, suggested that positive values of the function could indicate the higher individual risks. Indeed, all patients assigned to high risk by calculation were HPV infected and showed elevated viral E6, E7 mRNA concentration known to be associated with CC onset.
  
  
  CONCLUSIONS
  The research was concentrated on dynamical gene expression profiling upon pathological changes ultimately leading to CC. Differences of normalised mRNA concentrations were used for quantitative model design and its primary approbation.
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Bourmenskaya
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shubina
authors.forename: Dmitry
authors.initials: D
authors.lastname: Trofimov
authors.forename: Denis
authors.initials: D
authors.lastname: Rebrikov
authors.forename: Elina
authors.initials: E
authors.lastname: Sabdulaeva
authors.forename: Oksana
authors.initials: O
authors.lastname: Nepsha
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bozhenko
authors.forename: Svetlana
authors.initials: S
authors.lastname: Rogovskaya
authors.forename: Gennady
authors.initials: G
authors.lastname: Sukhikh
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D010641:Phenotype; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019562:Viral Load; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral