title: Gene expression signatures that classify the mode of invasion of primary oral squamous cell carcinomas.
abstract: To identify molecular signatures and establish a new diagnostic model for progressive oral squamous cell carcinoma (OSCC). Total RNAs were isolated from primary OSCCs from both node-positive and -negative patients and used in cDNA microarray analysis. To identify marker genes representing a malignant phenotype, their expression was further examined by quantitative reverse transcription-PCR (QRT-PCR) in 64 OSCC tissues. Using Fisher's linear discriminant analysis (LDA) fitted with a stepwise increment method, we created discriminatory predictor models. The stability of these models was examined using leave-one-out cross validation. Immunohistochemical analysis was performed. Among the 16,600 possible target cDNAs in the array analysis, 83 genes demonstrated significantly differential signals (>2-fold). We further identified 53 marker genes that can be implicated in the Yamamoto-Kohama's (YKs) mode of invasion for OSCCs (P < 0.06). Using LDA fitted with a stepwise increment method, we created four discriminatory predictor models based on 16- to 25-gene signatures which could best distinguish the five established grades of YKs mode of invasion. Leave-one out validation demonstrated that the stability of these models was 92-95%. For validation, we also examined an independent set of 13 primary OSCCs; the predictor models determined the invasion status from 77% to 100% (on average, 85%) fidelity with the pathological observations. TGM3 protein expression was markedly suppressed in highly invasive OSCCs. We reveal novel gene expression alterations during the progression of OSCC, and have constructed prediction models for the evaluation of the invasion status of these cancers.
authors.affiliation: Department of Biochemistry, Asahi University, School of Dentistry, Mizuho-shi, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kondoh
authors.forename: Toshio
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Shuri
authors.initials: S
authors.lastname: Ohkura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Arai
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Hada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shindoh
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ando
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Izumo
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Hitomi
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D016002:Discriminant Analysis; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction