Julia Schnoell1, Bernhard J Jank2, Lorenz Kadletz-Wanke1, Stefan Stoiber3,4, Clemens P Spielvogel3,5, Elisabeth Gurnhofer4, Lukas Kenner6,7,8,9, Gregor Heiduschka1. 1. Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria. 2. Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria. bernhard.jank@meduniwien.ac.at. 3. Christian Doppler Laboratory for Applied Metabolomics, Vienna, Austria. 4. Department of Pathology, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria. 5. Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria. 6. Christian Doppler Laboratory for Applied Metabolomics, Vienna, Austria. lukas.kenner@meduniwien.ac.at. 7. Department of Pathology, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria. lukas.kenner@meduniwien.ac.at. 8. Unit of Laboratory Animal Pathology, University of Veterinary Medicine, Vienna, Austria. lukas.kenner@meduniwien.ac.at. 9. CBmed GmbH-Center for Biomarker Research in Medicine, Graz, Styria, Austria. lukas.kenner@meduniwien.ac.at.
Abstract
PURPOSE: The transcription factors YY1 and CP2 have been associated with tumor promotion and suppression in various cancers. Recently, simultaneous expression of both markers was correlated with negative prognosis in cancer. The aim of this study was to explore the expression of YY1 and CP2 in head and neck squamous cell carcinoma (HNSCC) patients and their association with survival. METHODS: First, we analyzed mRNA expression and copy number variations (CNVs) of YY1 and CP2 using "The Cancer Genome Atlas" (TCGA) with 510 HNSCC patients. Secondly, protein expression was investigated via immunohistochemistry in 102 patients, who were treated in the Vienna General Hospital, utilizing a tissue microarray. RESULTS: The median follow-up was 2.9 years (1.8-4.6) for the TCGA cohort and 10.3 years (6.5-12.8) for the inhouse tissue micro-array (TMA) cohort. The median overall survival of the TCGA cohort was decreased for patients with a high YY1 mRNA expression (4.0 vs. 5.7 years, p = 0.030, corr. p = 0.180) and high YY1-CNV (3.53 vs. 5.4 years, p = 0.0355, corr. p = 0.213). Furthermore, patients with a combined high expression of YY1 and CP2 mRNA showed a worse survival (3.5 vs. 5.4 years, p = 0.003, corr. p = 0.018). The mortality rate of patients with co-expression of YY1 and CP2 mRNA was twice as high compared to patients with low expression of one or both (HR 1.99, 95% CI 1.11-3.58, p = 0.021). Protein expression of nuclear YY1 and CP2 showed no association with disease outcome in our inhouse cohort. CONCLUSION: Our data indicate that simultaneous expression of YY1 and CP2 mRNA is associated with shorter overall survival. Thus, combined high mRNA expression might be a suitable prognostic marker for risk stratification in HNSCC patients. However, since we could not validate this finding at genomic or protein level, we hypothesize that unknown underlying mechanisms which regulate mRNA transcription of YY1 and CP2 are the actual culprits leading to a worse survival.
PURPOSE: The transcription factors YY1 and CP2 have been associated with tumor promotion and suppression in various cancers. Recently, simultaneous expression of both markers was correlated with negative prognosis in cancer. The aim of this study was to explore the expression of YY1 and CP2 in head and neck squamous cell carcinoma (HNSCC) patients and their association with survival. METHODS: First, we analyzed mRNA expression and copy number variations (CNVs) of YY1 and CP2 using "The Cancer Genome Atlas" (TCGA) with 510 HNSCCpatients. Secondly, protein expression was investigated via immunohistochemistry in 102 patients, who were treated in the Vienna General Hospital, utilizing a tissue microarray. RESULTS: The median follow-up was 2.9 years (1.8-4.6) for the TCGA cohort and 10.3 years (6.5-12.8) for the inhouse tissue micro-array (TMA) cohort. The median overall survival of the TCGA cohort was decreased for patients with a high YY1 mRNA expression (4.0 vs. 5.7 years, p = 0.030, corr. p = 0.180) and high YY1-CNV (3.53 vs. 5.4 years, p = 0.0355, corr. p = 0.213). Furthermore, patients with a combined high expression of YY1 and CP2 mRNA showed a worse survival (3.5 vs. 5.4 years, p = 0.003, corr. p = 0.018). The mortality rate of patients with co-expression of YY1 and CP2 mRNA was twice as high compared to patients with low expression of one or both (HR 1.99, 95% CI 1.11-3.58, p = 0.021). Protein expression of nuclear YY1 and CP2 showed no association with disease outcome in our inhouse cohort. CONCLUSION: Our data indicate that simultaneous expression of YY1 and CP2 mRNA is associated with shorter overall survival. Thus, combined high mRNA expression might be a suitable prognostic marker for risk stratification in HNSCCpatients. However, since we could not validate this finding at genomic or protein level, we hypothesize that unknown underlying mechanisms which regulate mRNA transcription of YY1 and CP2 are the actual culprits leading to a worse survival.
Entities:
Keywords:
CP2; Head and neck squamous cell carcinoma; Prognosis; Survival; Transcription factor; YY1
Authors: David Seligson; Steve Horvath; Sara Huerta-Yepez; Stephanie Hanna; Hermes Garban; Alice Roberts; Tao Shi; Xueli Liu; David Chia; Lee Goodglick; Benjamin Bonavida Journal: Int J Oncol Date: 2005-07 Impact factor: 5.650