title: An Ultra-Deep Targeted Sequencing Gene Panel Improves the Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.
abstract: An improved prognostic stratification of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically positive (pN+) nodes is urgently needed. Here, we sought to examine whether an ultra-deep targeted sequencing (UDT-Seq) gene panel may improve the prognostic stratification in this patient group.A mutation-based signature affecting 10 genes (including genetic mutations in 6 oncogenes and 4 tumor suppressor genes) was devised to predict disease-free survival (DFS) in 345 primary tumor specimens obtained from pN+ OSCC patients. Of the 345 patients, 144 were extracapsular spread (ECS)-negative and 201 were ECS-positive. The 5-year locoregional control, distant metastases, disease-free, disease-specific, and overall survival (OS) rates served as outcome measures.The UDT-Seq panel was an independent risk factor (RF) for 5-year locoregional control (P = 0.0067), distant metastases (P = 0.0001), DFS (P < 0.0001), disease-specific survival (DSS, P < 0.0001), and OS (P = 0.0003) in pN+ OSCC patients. The presence of ECS and pT3-4 disease were also independent RFs for DFS, DSS, and OS. A prognostic scoring system was formulated by summing up the significant covariates (UDT-Seq, ECS, pT3-4) separately for each survival endpoint. The presence of a positive UDT-Seq panel (n = 77) significantly improved risk stratification for all the survival endpoints as compared with traditional AJCC staging (P < 0.0001). Among ECS-negative patients, those with a UDT-Seq-positive panel (n = 31) had significantly worse DFS (P = 0.0005) and DSS (P = 0.0002). Among ECS-positive patients, those with a UDT-Seq-positive panel (n = 46) also had significantly worse DFS (P = 0.0032) and DSS (P = 0.0098).Our UDT-Seq gene panel consisting of clinically actionable genes was significantly associated with patient outcomes and provided better prognostic stratification than traditional AJCC staging. It was also able to predict prognosis in OSCC patients regardless of ECS presence.
authors.affiliation: From the Department of Otorhinolaryngology, Head and Neck Surgery (C-TL, I-HC, K-PC, S-FH, C-JK), Department of Biomedical Sciences, School of Medicine (S-JC, H-CC), Department of Genomic Core Laboratory, Molecular Medicine Research Center (S-JC, H-CC), Department of Pathology (L-YL, CH), Department of Biostatistics and Informatics Unit, Clinical Trial Center (L-YY), Department of Radiation Oncology (C-YL, K-HF), Department of Medical Oncology (H-MW), Department of Diagnostic Radiology (S-HN), Department of Plastic and Reconstructive Surgery (C-HL, C-KT), Department of Nuclear Medicine and Molecular Imaging Center (T-CY), Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Lee
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Lan-Yan
authors.initials: LY
authors.lastname: Yang
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Kang-Hsing
authors.initials: KH
authors.lastname: Fan
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Shu-Hang
authors.initials: SH
authors.lastname: Ng
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Chung-Kan
authors.initials: CK
authors.lastname: Tsao
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Shiang-Fu
authors.initials: SF
authors.lastname: Huang
authors.forename: Chung-Jan
authors.initials: CJ
authors.lastname: Kang
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chen
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D009154:Mutation; D009367:Neoplasm Staging; D009857:Oncogenes / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate