Eps8 expression is significantly lower in p16+ head and neck squamous cell carcinomas (HNSCCs) compared with p16− HNSCCs

Nasri, Elham; Wiesen, Lisa; Knapik, Jacquelyn A.; Fredenburg, Kristianna M.

doi:10.1016/j.humpath.2017.10.021

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…(with prognostic efficacy), all of which were previously identified to play a major role in head and neck oncogenesis as well as in other cancers [45][46][47][48][49][50][51][52] EPS8, identified in ECS-laryngopharyngeal patients in this study, is known to be involved in the proliferation apoptosis, adhesion and migration in other cancers including HNSCC [53][54][55][56]. The correlation of these markers with the clinically/pathologically classified sub-cohorts (ALI+/PNI+) indicated their possible relevance as predictive panel, with a subset of genes providing survival impact.…”

Section: Discussionmentioning

confidence: 72%

Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach

2019

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Head and neck squamous cell carcinomas (HNSCC) includes multiple subsites that exhibit differential treatment outcome, which is in turn reflective of tumor stage/histopathology and molecular profile. This study hypothesized that the molecular profile is an accurate prognostic adjunct in patients triaged based on clinico-pathological characteristics. Towards this effect, publically available micro-array datasets (n = 8), were downloaded, classified based on HPV association (n = 83) and site (tongue n = 88; laryngopharynx n = 53; oropharynx n = 51) and re-analyzed (Genespring; v13.1). The significant genes were validated in respective cohorts in The Cancer Genome Atlas (TCGA) for correlation with clinico-pathological parameters/survival. The gene entities (n = 3258) identified from HPV based analysis, when validated in TCGA identified the subset specifically altered in HPV+ HNSCC (n = 63), with three genes showing survival impact (RPP25, NUDCD2, NOVA1). Site-specific meta-analysis identified respective differentials (tongue: 3508, laryngopharynx: 4893, oropharynx: 2386); validation in TCGA revealed markers with high incidence (altered in >10% of patients) in tongue (n = 331), laryngopharynx (n = 701) and oropharynx (n = 404). Assessment of these genes in clinical sub-cohorts of TCGA indicated that early stage tongue (MTFR1, C8ORF33, OTUD6B) and laryngeal cancers (TWISTNB, KLHL13 and UBE2Q1) were defined by distinct prognosticators. Similarly, correlation with perineural/angiolymophatic invasion, identified discrete marker panels with survival impact (tongue: NUDCD1, PRKC1; laryngopharynx: SLC4A1AP, PIK3CA, AP2M1). Alterations in ANO1, NUDCD1, PIK3CA defined survival in tongue cancer patients with nodal metastasis (node+ECS-), while EPS8 is a significant differential in node+ECS-laryngopharyngeal cancers. In oropharynx, wherein HPV is a major etiological factor, distinct prognosticators were identified in HPV+ (ECHDC2, HERC5, GGT6) and HPV-(GRB10, EMILIN1, FNDC1). Meta-analysis in combination with TCGA validation carried out in this study emphasized on the molecular heterogeneity inherent within HNSCC; the feasibility of leveraging this information for

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Section: Discussionmentioning

confidence: 72%

Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach

2019

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“…Moreover, expression profiles of p16 positive and p16 negative cancers might differ significantly emphasizing their different tumor behavior. So, it was shown that expression of Eps8 is different in these subtypes of HNSCC [33]. This EGFR substrate contributes to the carcinogenesis and might be involved in invasiveness in HNSCC [31].…”

Section: Discussionmentioning

confidence: 99%

“…This EGFR substrate contributes to the carcinogenesis and might be involved in invasiveness in HNSCC [31]. Interestingly, the expression of Eps8 correlated with the tumor stage and p16 status but not with anatomical localization of tumors [33]. Moreover, the expression of other histopathological parameters such as EGFR, VEGF, and NOTCH1 differ between p16 positive and negative tumors, which suggest differences in tumor angiogenesis in these entities [34].…”

Section: Discussionmentioning

confidence: 99%

Associations between Histogram Analysis Parameters Derived from DCE-MRI and Histopathological Features including Expression of EGFR, p16, VEGF, Hif1-alpha, and p53 in HNSCC

Meyer¹,

Leifels²,

Hamerla³

et al. 2019

Contrast Media & Molecular Imaging

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Background Our purpose was to elucidate possible correlations between histogram parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) with several histopathological features in head and neck squamous cell carcinomas (HNSCC). Methods Thirty patients with primary HNSCC were prospectively acquired. Histogram analysis was derived from the DCE-MRI parameters: Ktrans, Kep, and Ve. Additionally, in all cases, expression of human papilloma virus (p16) hypoxia-inducible factor-1-alpha (Hif1-alpha), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and tumor suppressor protein p53 were estimated. Results K ep kurtosis was significantly higher in p16 tumors, and Ve min was significantly lower in p16 tumors compared to the p16 negative tumors. In the overall sample, Kep entropy correlated well with EGFR expression (p=0.38, P=0.04). In p16 positive carcinomas, Ktrans max correlated with VEGF expression (p=0.46, P=0.04), Ktrans kurtosis correlated with Hif1-alpha expression (p=0.46, P=0.04), and Ktrans entropy correlated with EGFR expression (p=0.50, P=0.03). Regarding Kep parameters, mode correlated with VEGF expression (p=0.51, P=0.02), and entropy correlated with Hif1-alpha expression (p=0.47, P=0.04). In p16 negative carcinomas, Kep mode correlated with Her2 expression (p=−0.72, P=0.03), Ve max correlated with p53 expression (p=−0.80, P=0.009), and Ve p10 correlated with EGFR expression (p=0.68, P=0.04). Conclusion DCE-MRI can reflect several histopathological features in HNSCC. Associations between DCE-MRI and histopathology in HNSCC depend on p16 status. Kep kurtosis and Ve min can differentiate p16 positive and p16 negative carcinomas.

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“…The earliest studies reported that Eps8 overexpression encodes cell growth in fibroblasts (7), and its potential role in the development of human cancer has gradually been confirmed. Eps8 mRNA expression levels are sequentially increased in primary tumours, metastases, and malignant ascites, and Eps8 mRNA is predominantly expressed in advanced colorectal cancer (84). Similarly, Eps8 overexpression is highly associated with lymph node metastasis and parametrium invasion of cervical cancer (14).…”

Section: Role and Mechanisms Of Eps8 In Tumour Invasion And Metastasismentioning

confidence: 99%

Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review)

et al. 2021

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Epidermal growth factor receptor pathway substrate 8 (Eps8) was initially identified as the substrate for the kinase activity of EGFR, improving the responsiveness of EGF, which is involved in cell mitosis, differentiation and other physiological functions. Numerous studies over the last decade have demonstrated that Eps8 is overexpressed in most ubiquitous malignant tumours and subsequently binds with its receptor to activate multiple signalling pathways. Eps8 not only participates in the regulation of malignant phenotypes, such as tumour proliferation, invasion, metastasis and drug resistance, but is also related to the clinicopathological characteristics and prognosis of patients. Therefore, Eps8 is a potential tumour diagnosis and prognostic biomarker and even a therapeutic target. This review aimed to describe the structural characteristics, role and related molecular mechanism of Eps8 in malignant tumours. In addition, the prospect of Eps8 as a target for cancer therapy is examined.

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Eps8 expression is significantly lower in p16+ head and neck squamous cell carcinomas (HNSCCs) compared with p16− HNSCCs

Cited by 6 publications

References 24 publications

Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach

Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach

Associations between Histogram Analysis Parameters Derived from DCE-MRI and Histopathological Features including Expression of EGFR, p16, VEGF, Hif1-alpha, and p53 in HNSCC

Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review)

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