Analysis of gene copy number changes in head and neck cancer

Baltaci, Elif; Karaman, Emin; Dalay, Nejat; Buyru, Nur

doi:10.1111/coa.12686

Cited by 15 publications

(19 citation statements)

References 28 publications

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“…Members of the NET (for NocA, Nlz, Elbow, and TLP-1) family have recently been shown to play important roles in embryonic development and tumour progression [9, 10]. It has been shown that ZNF703 is overexpressed in several types of malignancies, including breast cancer [11], lung cancer [12], gastric cancer [13], colorectal cancer [14] and cholangiocarcinoma [15], and its high expression promotes the progression of these cancers.…”

Section: Introductionmentioning

confidence: 99%

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

Wang

Deng

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Zinc finger protein 703 (ZNF703), initially identified as a novel oncogene in human breast cancer, is a member of the NET/NlZ family of zinc finger transcription factors. It is recognized that the overexpression of ZNF703 is associated with various types of human cancers, but the role and molecular mechanism of ZNF703 in oral squamous cell carcinoma (OSCC) are unknown. Methods: ZNF703 expression levels were examined in OSCC tissues and non-cancerous tissues by qRT-PCR and immunohistochemistry (IHC). The molecular mechanisms of ZNF703 and its effects on cell growth and metastasis were explored in vitro and in vivo using the CCK8 assay, colony formation assay, cell cycle analysis, migration and invasion assays, wound-healing assay, western blotting and xenograft experiments in nude mice. Results: In this study, ZNF703 was found to be upregulated in OSCC tissues compared to that in normal tissues at both mRNA and protein levels, and its expression level was closely correlated with the overall survival of patients with OSCC. Silencing of the ZNF703 gene in OSCC cells significantly inhibited cell growth and metastasis in vitro and in vivo. Conversely, the overexpression of ZNF703 in OSCC cells promoted cancer growth and metastasis in vitro. Mechanistically, ZNF703 activated the PI3K/AKT/GSK-3β signalling pathway and its downstream effectors, thus regulating the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, the promotive effects of ZNF703 on cellular proliferation and metastasis could be rescued by LY294002 (a PI3K-specific inhibitor) and MK2206 (an Akt-specific inhibitor). Conclusion: The results show that ZNF703 promotes cell growth and metastasis through PI3K/Akt/GSK-3β signalling in OSCC and that it may be a promising target in the treatment of patients with OSCC.

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Section: Introductionmentioning

confidence: 99%

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

Wang

Deng

Zhang

et al. 2017

Cell Physiol Biochem

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“…They also indicated that ZNF703 expression can be induced by CCND1 expression. In our previous study, we identified ZNF703 and CCND1 amplification in 18% and 24% of the HNSCC tumours, respectively . Therefore, in this study to evaluate the effect of gene amplification on mRNA expression and crosstalk between ZNF703 and CCND1 in HNSCC, we analysed the association between the expression rates of these genes in HNSCC tumour samples.…”

Section: Introductionmentioning

confidence: 95%

ZNF703 is an important player in head and neck cancer

Orhan

Bakir

Dalay

et al. 2019

Clinical Otolaryngology

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Objectives Despite advances in treatment, head and neck squamous cell carcinoma (HNSCC) remains difficult to treat and the overall survival rate has only modestly improved over the past years. Therefore, there is a need to understand the molecular mechanism of HNSCC. Zinc finger protein 703 (ZNF703) is an oncogenic transcription factor, and ZNF703 gene expression is altered in many cancers as a result of chromosome 8p12 amplification. The purpose of this study was to investigate the expression pattern of ZNF703 in HNSCC in association with CCND1 expression and Akt phosphorylation. Design Prospective study. Setting University hospital. Participants One hundred and five patients with HNSCC. Methods Fifty HNSCC tumour and non‐cancerous tissue samples were investigated by qRT‐PCR and Western blotting. Results ZNF703 gene expression was increased in 22.9% of tumour tissues compared with its normal counterparts. The results were correlated with clinicopathological features, copy number variation and survival data. Conclusion ZNF703 over‐expression is associated with copy number variation and this over‐expression may activate PI3K/Akt signalling pathway in HNSCC.

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“…Among the key prognostic markers for survival, epidermal growth factor receptor (EGFR), cyclin D1(CCND1), ERCC1, p16, human papillomavirus (HPV), and B‐cell lymphoma‐extra large (Bcl‐xL)/Bcl‐2, as well as the amplification of genes including EMS1 , FGFR1 , and CCND1 have demonstrated some evidence in clinical trials. Others are slower to advance in clinical development because of unconvincing data and few published studies; for example, acetylcholinesterase(AchE), SNPs of specific genes, glutathione S‐transferase (GST), CD44, amplification of specific genes, hypoxic markers, KLK‐6, and MDA‐7/IL‐24; although, this does not preclude them from future investigations and clinical utility.…”

Section: Biomarkers In Hnscc Tumor Tissuesmentioning

confidence: 99%

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

Hsieh

Wang

et al. 2019

Head & Neck

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Background Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies. Methods Recent, relevant peer‐reviewed evidence were critically reviewed and summarized. Results This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed. Conclusion Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies.

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Analysis of gene copy number changes in head and neck cancer

Cited by 15 publications

References 28 publications

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma

ZNF703 is an important player in head and neck cancer

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

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