Transcription factors CP2 and YY1 as prognostic markers in head and neck squamous cell carcinoma: analysis of The Cancer Genome Atlas and a second independent cohort

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.

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The prognostic value of faciogenital dysplasias as biomarkers in head and neck squamous cell carcinoma

Biomarkers in Medicine ◽

10.2217/bmm-2019-0273 ◽

2019 ◽

Vol 13 (16) ◽

pp. 1399-1415 ◽

Cited By ~ 1

Author(s):

Chao Ma ◽

Haoyu Li ◽

Xian Li ◽

Shuwen Lu ◽

Jianfeng He

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Value ◽

The Cancer Genome Atlas ◽

Gene Expressions ◽

Cancer Genome Atlas ◽

Genome Atlas

Aim: This present study aims to investigate the prognostic value of FGD genes for predicting the overall survival in head and neck squamous cell carcinoma (HNSC) patients. Materials & methods: Clinical information and FGD gene expressions of 513 HNSC patients were obtained from The Cancer Genome Atlas dataset. Kaplan–Meier survival, Pearson correlation coefficient analyses and enrichment analyses were performed based on The Cancer Genome Atlas dataset, as well as FGD gene expressions analysis in normal tissues. Results: The survival analyses showed that high levels of FGD2 and FGD3 mRNA expressions, and the combination of high levels of FGD2 and FGD3 mRNAs were associated with the favorable overall survival in HNSC patients (p < 0.01). Oppositely, no significant correlations (p > 0.05) were observed between gender and race and OS. Conclusion: Our findings suggest that the expression levels of FGD2 and FGD3 mRNAs in HNSC are associated with favorable prognosis and may be regarded as potential prognostic biomarkers.

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A MicroRNA Expression Signature as Prognostic Marker for Oropharyngeal Squamous Cell Carcinoma

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa161 ◽

2020 ◽

Author(s):

Xinyi Liu ◽

Ping Liu ◽

Rebecca D Chernock ◽

Zhenming Yang ◽

Krystle A Lang Kuhs ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Risk Group ◽

The Cancer Genome Atlas ◽

Mirna Signature ◽

Independent Validation ◽

Cancer Genome Atlas ◽

Genome Atlas

Abstract Background Improved prognostication of oropharyngeal squamous cell carcinoma (OPSCC) may facilitate individualized patient management. The goal of this study was to develop and validate a prognostic signature based on microRNA sequencing (miRNA-seq) analysis. Methods We collected tumor specimens for miRNA-seq analysis from OPSCC patients treated at Washington University in St Louis (n = 324) and Vanderbilt University (n = 130). OPSCC patients (n = 79) from The Cancer Genome Atlas Program were also included for independent validation. Univariate and multivariable Cox regression analyses were performed to identify miRNAs associated with disease outcomes. All statistical tests were 2-sided. Results By miRNA-seq profiling analysis, we identified a 26-miRNA signature. Based on computed risk scores of the signature, we classified the patients into low- and high-risk groups. In the training cohort, the high-risk group had much shorter overall survival compared with the low-risk group (hazard ratio [HR] = 3.80, 95% confidence interval [CI] = 2.37 to 6.10, P < .001). Subgroup analysis further revealed that the signature was prognostic for HPV-positive OPSCCs (HR = 3.07, 95% CI = 1.65 to 5.71, P < .001). Multivariable analysis indicated that the signature was independent of common clinicopathologic factors for OPSCCs. Importantly, the miRNA signature was a statistically significant predictor of overall survival in independent validation cohorts (The Cancer Genome Atlas Program cohort: HR = 6.05, 95% CI = 2.10 to 17.37, P < .001; Vanderbilt cohort: HR = 7.98, 95% CI = 3.99 to 15.97, P < .001; Vanderbilt HPV-positive cohort: HR = 8.71, 95% CI = 2.70 to 28.14, P < .001). Conclusions The miRNA signature is a robust and independent prognostic tool for risk stratification of OPSCCs including HPV-positive OPSCCs.

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Genomic Landscape of Squamous Cell Carcinoma of the Lung

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2013.33.348 ◽

2013 ◽

pp. 348-353

Author(s):

Daniel Morgensztern ◽

Siddhartha Devarakonda ◽

Ramaswamy Govindan

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Targets ◽

The Cancer Genome Atlas ◽

Molecular Alterations ◽

The Past ◽

Genomic Landscape ◽

Cancer Genome Atlas ◽

Genome Atlas

Outcomes with standard therapy for patients with advanced squamous cell carcinoma (SQCC) of the lung have not improved significantly over the past decade using a predominantly empiric approach. Recent advances in pulmonary adenocarcinomas (ACs) have allowed the subdivision according to molecular subsets and the identification of specific molecular alterations that predict significant benefit from specific targeted therapies. Genomic alterations reported by The Cancer Genome Atlas (TCGA) Project identified a number of molecular targets that need to be studied systematically to improve the overall survival of patients with SQCC of the lung.

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