Protumor role of estrogen receptor expression in oral squamous cell carcinoma cells

Akyu, Rie; Tomihara, Kei; Yamazaki, Manabu; Moniruzzaman, Rohan; Heshiki, Wataru; Sekido, Katsuhisa; Tachinami, Hidetake; Sakurai, Kotaro; Yonesi, Amirmoezz; Imaue, Shuichi; Fujiwara, Kumiko; Noguchi, Makoto

doi:10.1016/j.oooo.2021.04.006

Cited by 11 publications

(13 citation statements)

References 43 publications

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“…Oral squamous cell carcinoma (OSCC) is the leading cause of cancer-related deaths worldwide [ 16 ]. Extensive lymph node metastasis in OSCC is associated with low survival rates.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Comprehensive and Integrated Analysis Identifies ZEB1 as a Key Novel Gene in Oral Squamous Cell Carcinoma

Tao

et al. 2022

Contrast Media & Molecular Imaging

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Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with a poor prognosis. Therefore, it is crucial to explore molecular prognostic biomarkers for OSCC. ZEB1 (also known as δEF1) is a member of the zinc finger E-box binding protein family of transcription factors involved in various biological processes, including tumorigenesis, progression, and metastasis. Recent evidence suggests that ZEB1 has a role in the tumorigenicity of oral epithelial cells, although its mode of action needs to be investigated further. To better understand the relationship between ZEB1 and OSCC, we transfected the ZEB1-overexpressing oral squamous cell lines SCC9 and SCC25 with lentivirus and then extracted RNA from the cells for gene expression analysis. Furthermore, the GSE30784 dataset was downloaded from the Gene Expression Omnibus (GEO) database to identify potential biomarkers of OSCC and to assess the potential mechanisms. The criteria for identification of their DEGs were |logFC| > 1 and P < 0.05. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were also carried out. Integrating the data from the PPI network and survival analysis identified that ZEB1 might be an independent prognostic biomarker in OSCC. In conclusion, integrated bioinformatics and microarray analysis identified the critical gene ZEB1 linked to the overall survival (OS) of patients with OSCC. ZEB1 could be applied as a prognostic biomarker to forecast the survival of patients with OSCC and might indicate innovative therapeutic indicators for OSCC.

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“…Oral squamous cell carcinoma (OSCC) is the leading cause of cancer-related deaths worldwide [ 16 ]. Extensive lymph node metastasis in OSCC is associated with low survival rates.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Comprehensive and Integrated Analysis Identifies ZEB1 as a Key Novel Gene in Oral Squamous Cell Carcinoma

Tao

et al. 2022

Contrast Media & Molecular Imaging

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“…Information about the immunohistochemical expression of ERα and ERβ in OSCC primary tissue is rare and remains controversial. In most studies, including a study from our study group, ERβ was found to be the predominant sub-type in OSCC primary tissues [ 19 , 21 , 24 , 28 ].…”

Section: Discussionmentioning

confidence: 91%

“…In contrast to other studies [ 19 , 21 , 24 , 26 , 27 , 28 ], one strength of this study is the analysis of ERα in a comparatively high number of patients in a homogenous cohort of OSCC. The main points of criticism are the retrospective data collection and the evaluation of ERα on tissue microarrays.…”

Section: Discussionmentioning

confidence: 98%

“…The prevalence for ERα when evaluating (paraffin-embedded) OSCC tissue ranges from 0 to 13% [ 19 , 21 , 24 , 26 , 27 , 28 ]. A study published by Egloff et al revealed an ERα positivity of 95% in 56 head and neck tumors that were evaluated (including 23 OSCC); however, detailed information only for the OSCC cohort was not reported [ 20 ]; therefore, a direct comparison is not possible.…”

Section: Discussionmentioning

confidence: 99%

“…In general, information about the immunohistochemical expression of ERα in OSCC primary tissues is rare and remains controversial. The prevalence of ERα when evaluating (paraffin-embedded) OSCC tissue ranges from 0 to 13% [ 19 , 21 , 24 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma

Doll

Bestendonk

Kreutzer

et al. 2021

Cancers

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Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.

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Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study

et al. 2023

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Background: Some oral squamous cell carcinoma (OSCC) cases are unaffected by smoking or drinking. This study aimed to clarify distinctive groups among OSCC patients and examine the characteristics of multiple primary carcinomas (MPCs).Methods: We analyzed data from 970 patients. The patients were divided into three groups: all individuals <45 years (<45 y), smokers/drinkers ≥45 years (SD ≥45 y), and non-smokers/non-drinkers ≥45 years (NSND ≥45 y).

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Protumor role of estrogen receptor expression in oral squamous cell carcinoma cells

Cited by 11 publications

References 43 publications

[Retracted] Comprehensive and Integrated Analysis Identifies ZEB1 as a Key Novel Gene in Oral Squamous Cell Carcinoma

[Retracted] Comprehensive and Integrated Analysis Identifies ZEB1 as a Key Novel Gene in Oral Squamous Cell Carcinoma

Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma

Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study

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