title: Four-gene expression model predictive of lymph node metastases in oral squamous cell carcinoma.
abstract: BACKGROUND
  Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue.
  
  
  METHODS
  We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients.
  
  
  RESULTS
  Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN +) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN + with an accuracy of 80.0% (p = 0.012).
  
  
  CONCLUSIONS
  The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our "Nodal Index" model are predictive of lymph node metastasis in OSCC.
authors: Disciplina de Oncologia, Departamento Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo, Brazil. fatima@lim24.fm.usp.br
authors: Fátima Solange
authors: FS
authors: Pasini
authors: Simone
authors: S
authors: Maistro
authors: Igor
authors: I
authors: Snitcovsky
authors: Lílian P
authors: LP
authors: Barbeta
authors: Flavia R
authors: FR
authors: Rotea Mangone
authors: Carlos N
authors: CN
authors: Lehn
authors: Fernando
authors: F
authors: Walder
authors: Marcos B
authors: MB
authors: Carvalho
authors: M Mitzi
authors: MM
authors: Brentani
authors: Miriam H H
authors: MH
authors: Federico
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D002352:Carrier Proteins / Q000378:metabolism*; D048128:Casein Kinase Ialpha / Q000378:metabolism*; D055233:Cornified Envelope Proline-Rich Proteins / Q000378:metabolism*; D004265:DNA Helicases; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D008207:Lymphatic Metastasis; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D055233:Cornified Envelope Proline-Rich Proteins; D005819:Genetic Markers; D051907:Lysosomal Membrane Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; C491986:SPRR2B protein, human; D048128:Casein Kinase Ialpha; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases