title: An eleven gene molecular signature for extra-capsular spread in oral squamous cell carcinoma serves as a prognosticator of outcome in patients without nodal metastases.
abstract: OBJECTIVE
  Extracapsular spread (ECS) is an important prognostic factor for oral squamous cell carcinoma (OSCC) and is used to guide management. In this study, we aimed to identify an expression profile signature for ECS in node-positive OSCC using data derived from two different sources: a cohort of OSCC patients from our institution (National Cancer Centre Singapore) and The Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) cohort. We also sought to determine if this signature could serve as a prognostic factor in node negative cancers.
  
  
  METHODS
  Patients with a histological diagnosis of OSCC were identified from an institutional database and fresh tumor samples were retrieved. RNA was extracted and gene expression profiling was performed using the Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. RNA sequence data and corresponding clinical data for the TCGA HNSCC cohort were downloaded from the TCGA Data Portal. All data analyses were conducted using R package and SPSS.
  
  
  RESULTS
  We identified an 11 gene signature (GGH, MTFR1, CDKN3, PSRC1, SMIM3, CA9, IRX4, CPA3, ZSCAN16, CBX7 and ZFP3) which was robust in segregating tumors by ECS status. In node negative patients, patients harboring this ECS signature had a significantly worse overall survival (p=0.04).
  
  
  CONCLUSIONS
  An eleven gene signature for ECS was derived. Our results also suggest that this signature is prognostic in a separate subset of patients with no nodal metastasis Further validation of this signature on other datasets and immunohistochemical studies are required to establish utility of this signature in stratifying early stage OSCC patients.
authors.affiliation: Department of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Weining
authors.initials: W
authors.lastname: Wang
authors.affiliation: Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Weng Khong
authors.initials: WK
authors.lastname: Lim
authors.affiliation: Cancer Therapeutics Research Laboratory, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Hui Sun
authors.initials: HS
authors.lastname: Leong
authors.affiliation: Cancer Therapeutics Research Laboratory, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Fui Teen
authors.initials: FT
authors.lastname: Chong
authors.affiliation: Department of Pathology, Singapore General Hospital, Outram Road, Singapore 169610, Singapore.
authors.forename: Tony K H
authors.initials: TK
authors.lastname: Lim
authors.affiliation: Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; Department of Medical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Daniel S W
authors.initials: DS
authors.lastname: Tan
authors.affiliation: Cancer Therapeutics Research Laboratory, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.affiliation: Department of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; Cancer Therapeutics Research Laboratory, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore. Electronic address: gopaliyer@yahoo.com.
authors.forename: N Gopalakrishna
authors.initials: NG
authors.lastname: Iyer
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000235:genetics*; D011379:Prognosis
keywords: Extracapsular spread; Gene molecular signature; Oral squamous cell carcinoma; Prognostic factor