Expression and influence of Notch signaling in oral squamous cell carcinoma

Osathanon, Thanaphum; Nowwarote, Nunthawan; Pavasant, Prasit

doi:10.2334/josnusd.15-0535

Cited by 27 publications

(26 citation statements)

References 58 publications

(74 reference statements)

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“…Site-specific meta-analysis of publicly available data identified a subset of genes that were common across the three major sites of HNSCC (tongue, laryngopharynx, oropharynx); the pathways that were primarily enriched included focal adhesion and proteoglycans in cancer, and cell cycle, mitotic pathway, which are well known in various cancers [29][30][31][32][33][34][35][36][37]. Differential expression profiling of the tongue cancer cohort triaged based on the stage, pathology identified multiple candidate markers; JAM2, SMURF1, LY6E, MFN1 and SUPT16H.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

2019

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“…6 Surgical resection is one of the treatment options of OSCC. Margin assessment is indeed an essential prognostic factor.…”

Section: Introductionmentioning

confidence: 99%

Inflammation related genes are upregulated in surgical margins of advanced stage oral squamous cell carcinoma

Suwanwela

Osathanon

2017

Journal of Oral Biology and Craniofacial Research

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A B S T R A C TAims: Advanced stage of oral squamous cell carcinoma (OSCC) exhibits different properties compared with the early stage for example an invasion ability. The present study investigated a differential gene expression of surgical margin between advanced and early stage of OSCC. Methods: Gene Expression Omnibus dataset (GSE31056) was downloaded and re-analyzed. Surgical margin samples were categorized into 2 groups; early stage and late stage. Differential gene expression analysis was performed. Dysregulated genes were further analyzed for gene ontology, enriched pathway, and disease association using a network-based analysis tools. Results: Eighty-five dysregulated genes were identified in margin of late stage OSCC. Metabolic process and biological regulation were the main gene ontology of dysregulated genes. Genes involved in Jak-STAT signaling pathway were upregulated in late stage of surgical margin samples. In addition, seven upregulated genes in late stage group, namely CEBPB, S1PR1, IL6, CEBPD, CHI3L1, PTX3, and SOCS3, were categorized in acute phase reaction and inflammation categories of disease association analysis. Conclusion: The differential expressed genes in surgical margin of late stage OSCC could be further employed to understand cancer's behavior and to identify target pathway to prevent OSCC invasion.

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“…Chen et al (2009) showed that NUMB expression increased during cervical carcinogenesis [ 24 ]. Increased NUMB expression has also been reported in oral squamous cell carcinoma (OSCC) [ 31 ], hepatocellular cancer (HCC) [ 35 ] and endometrial cancer [ 36 ]. In contrast, other studies have suggested NUMB as a tumor suppressor protein [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Loss of nuclear NOTCH1, but not its negative regulator NUMB, is an independent predictor of cervical malignancy

et al. 2018

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The participation of NOTCH signaling in invasive cervical cancer (ICC) remains controversial since both tumor suppressive and oncogenic properties have been described. Additionally, the role of NUMB, a negative regulator of NOTCH, remains unclear in ICC. We aimed to investigate the role of NOTCH1 and NUMB expression and their localization in cervical intraepithelial neoplasia (CIN) and ICC samples. A total of 144 biopsies were obtained from the Instituto Nacional de Cancerología, México from 2004 to 2017, and were subjected to immunohistochemistry for NOTCH1 and NUMB. We found that nuclear NOTCH1 expression was more frequently found in CIN samples compared with ICC (77.55% vs. 15.79%, p = 0.001). NUMB was almost exclusively found in the nucleus of CIN samples (32.65% vs. 6.32%, p = 0.001). Cytoplasmic expression of NOTCH1 (44.21%) and NUMB (35.79%) was the most frequent localization in ICC. Multivariable-adjusted analysis showed that the loss of nuclear NOTCH1 expression was an independent predictor of malignancy (β = –3.428, 95% confidence interval [95% CI] = –5.127, –1.728, p = 0.001). In contrast, the association between cytoplasmic NUMB expression and cervical cancer was lost after adjusting for nuclear NOTCH1 expression (β = 2.074, 95% [CI] = –0.358, 4.506, P = 0.094). Additionally, patients with cytoplasmic NOTCH1 expression showed a borderline association with longer overall survival (OS) than those with nuclear NOTCH1 expression (P = 0.08). Our data suggest that the loss of nuclear NOTCH1 but not NUMB might be an independent predictor of malignancy in cervical cancer.

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Expression and influence of Notch signaling in oral squamous cell carcinoma

Cited by 27 publications

References 58 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

Inflammation related genes are upregulated in surgical margins of advanced stage oral squamous cell carcinoma

Loss of nuclear NOTCH1, but not its negative regulator NUMB, is an independent predictor of cervical malignancy

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