Miguel Angel Pavón1,2, Matilde Parreño3, Marta Téllez-Gabriel1,2, Xavier León2,4, Irene Arroyo-Solera1,2, Montserrat López4, Maria Virtudes Céspedes1,2, Isolda Casanova1,2, Alberto Gallardo5, Antonio López-Pousa2,6, Maria Antonia Mangues7, Miquel Quer4, Agustí Barnadas6, Ramón Mangues1,2. 1. Grup d'Oncogènesi i Antitumorals (GOA), Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau (HSCSP), Barcelona, Spain. 2. Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain. 3. Translational Molecular Oncology, IIB-Sant Pau, HSCSP, Barcelona, Spain. 4. Department of Otorhinolaryngology, IIB-Sant Pau, HSCSP, Barcelona, Spain. 5. Department of Pathology, Clínica Girona, Girona, Spain. 6. Department of Medical Oncology, IIB-Sant Pau, HSCSP, Barcelona, Spain. 7. Department of Pharmacy, IIB-Sant Pau, HSCSP, Barcelona, Spain.
Abstract
BACKGROUND: We studied the association between the expression of a subset of previously identified genes and clinical outcome in patients with head and neck cancer. METHODS: We analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of 89 genes in tumor biopsies from stage III to IVa/b chemotherapy treated patients (n = 46). Two additional cohorts analyzed by RNAseq (The Cancer Genome Atlas [TCGA] project; n = 371) or immunohistochemistry (IHC; n = 73) were used to validate results. RESULTS: Thirty genes were associated with local-recurrence or progression-free survival. The best multi-gene decision-tree model to predict local recurrence included nuclear receptor coactivator 1 (NCOA1) and serum-amyloid A2 (SAA2) expression, whereas the best model to predict disease recurrence included creatine kinase mitochondrial 1 (CKMT1) and metal-regulatory transcription factor 1 (MTF1). Both models were associated with cancer-specific survival. Results were confirmed analyzing the RNAseq data included in the TCGA project. CKMT1 and NCOA1 were identified as independent risk factors for survival in an independent cohort analyzed by immunohistochemistry. CONCLUSION: CKMT1 and NCOA1 expression has prognostic significance in advanced-stage head and neck carcinoma.
BACKGROUND: We studied the association between the expression of a subset of previously identified genes and clinical outcome in patients with head and neck cancer. METHODS: We analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of 89 genes in tumor biopsies from stage III to IVa/b chemotherapy treated patients (n = 46). Two additional cohorts analyzed by RNAseq (The Cancer Genome Atlas [TCGA] project; n = 371) or immunohistochemistry (IHC; n = 73) were used to validate results. RESULTS: Thirty genes were associated with local-recurrence or progression-free survival. The best multi-gene decision-tree model to predict local recurrence included nuclear receptor coactivator 1 (NCOA1) and serum-amyloid A2 (SAA2) expression, whereas the best model to predict disease recurrence included creatine kinase mitochondrial 1 (CKMT1) and metal-regulatory transcription factor 1 (MTF1). Both models were associated with cancer-specific survival. Results were confirmed analyzing the RNAseq data included in the TCGA project. CKMT1 and NCOA1 were identified as independent risk factors for survival in an independent cohort analyzed by immunohistochemistry. CONCLUSION:CKMT1 and NCOA1 expression has prognostic significance in advanced-stage head and neck carcinoma.