Abstract
PurposeThe 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.MethodsFirst, 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.ResultsThe 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.ConclusionOur 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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide and about 650,000 new cases are diagnosed each year (Cognetti et al 2008).The reported 5-year survival rates range between 25 and59% and strongly depend on the anatomic site and stage at presentation (Gatta et al 2015)
The median overall survival of the The Cancer Genome Atlas” (TCGA) cohort was decreased for patients with a high Ying Yang 1 (YY1)
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)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide and about 650,000 new cases are diagnosed each year (Cognetti et al 2008).The reported 5-year survival rates range between 25 and59% and strongly depend on the anatomic site and stage at presentation (Gatta et al 2015). Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide and about 650,000 new cases are diagnosed each year (Cognetti et al 2008). The reported 5-year survival rates range between 25 and. Therapy has evolved and survival rates have improved, about one-third of patients die within 5-years of diagnosis (Pulte and Brenner 2010). Known risk factors for poor survival are smoking, poor socioeconomic status and a negative human papilloma virus (HPV) status in oropharyngeal SCC patients (Gatta et al 2015). While treatment de-escalation is currently under clinical investigation in HPV-positive oropharyngeal SCC patients, biomarkers for better therapeutic decision guidance in HNSCC are still lacking (Mirghani and Blanchard 2018)
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