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Estrogen receptor ? and ? in esophageal squamous cell carcinoma.

ABSTRACT: A gender difference has been reported in the morbidity of esophageal squamous cell carcinoma (ESCC). Estrogens have been proposed to play a role in this difference but the details have not yet been clarified. Therefore, in the present study, we examined the status of estrogen receptor (ER)? and ER? in 90 Japanese ESCC patients. ER? and ER? immunoreactivity was detected in the nuclei of ESCC cells (41.1 and 97.8%, respectively). There was a significant positive association between the ER? H score and histological differentiation (P = 0.0403), TNM-pM (LYM) (P = 0.00164) and Ki67/MIB1 LI of carcinoma cells (P = 0.0497, r = 0.207). In addition, the ER? status of carcinoma cells was significantly correlated with unfavorable clinical outcome of the patients. Multivariate analysis further revealed the ER? status in carcinoma cells as an independent unfavorable prognostic factor of these patients. We further examined the effects of estrogen treatment on ESCC cell line (ECGI-10) transfected with ER? or ER? in vitro. The number of ECGI-10 transfected with ER? was increased by estradiol or ER? specific agonist but estradiol did not exert any effect upon the cell number of ECGI-10 transfected with ER?. In summary, the results of the present study clearly demonstrate that the status of ER? in ESCC was closely associated with the unfavorable prognosis, possibly through altering cell proliferation of carcinoma cells.

SUBMITTER: Zuguchi M

PROVIDER: S-EPMC7659275 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Estrogen receptor α and β in esophageal squamous cell carcinoma.

Zuguchi Masashi M Miki Yasuhiro Y Onodera Yoshiaki Y Fujishima Fumiyoshi F Takeyama Daisuke D Okamoto Hiroshi H Miyata Go G Sato Akira A Satomi Susumu S Sasano Hironobu H

Cancer science 20120515 7

A gender difference has been reported in the morbidity of esophageal squamous cell carcinoma (ESCC). Estrogens have been proposed to play a role in this difference but the details have not yet been clarified. Therefore, in the present study, we examined the status of estrogen receptor (ER)α and ERβ in 90 Japanese ESCC patients. ERα and ERβ immunoreactivity was detected in the nuclei of ESCC cells (41.1 and 97.8%, respectively). There was a significant positive association between the ERβ H score ...[more]

PMID: 22463081

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Project description:BackgroundEstrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.ResultsBased on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.ConclusionTo the best of our knowledge our study is the first to use a cancer disease model as the framework to identify hormone responsive genes. Although we used ESCC as the disease model and estrogen as the hormone, the methodology can be extended analogously to other diseases as the model and other hormones. We believe that our results provide useful information for those interested in genes responsive to hormones and in the design of hormone-based therapies.

Project description:The tumor immune response is dependent on the interaction between tumor cells and the T-cell subset expressing the T-cell receptor (TCR) repertoire that infiltrates into the tumor microenvironment. The present study explored the diversity and shared TCR repertoires expressed on the surface of locoregional T cells and identified the T lymphocyte subsets infiltrating into esophageal squamous cell carcinoma (ESCC), in order to provide insight into the efficiency of immunotherapy and the development of a novel immune-oriented therapeutic strategy. A total of 53 patients with ESCC were enrolled in the present study, and immunohistochemical analysis of CD3, CD8, CD45RO, FOXP3, CD274, HLA class I and AE1/AE3 was performed. Digital pathological assessment was performed to evaluate the expression level of each marker. The clinicopathological significance of the immuno relation high (IR-Hi) group was assessed. Adaptor ligation PCR and next-generation sequencing were performed to explore the diversity of the TCR repertoire and to investigate the shared TCR repertoire in the IR-Hi group. Repertoire dissimilarity index (RDI) analysis was performed to assess the diversity of TCR, and the existence of shared TCRα and TCRβ was also investigated. Further stratification was performed according to the expression of markers of different T-cell subsets. Patients were stratified into IR-Hi and immuno relation low (IR-Lo) groups. Cancer-specific survival and recurrence-free survival rates were significantly improved in the IR-Hi group compared with in the IT-Lo group. The diversity of the TCR repertoire was significantly higher in the IR-Hi group. TCR repertoire analysis revealed 27 combinations of TCRα and 23 combinations of TCRβ VJ regions that were shared among the IR-Hi group. The IR-Hi group was divided into three clusters. Overall, the current findings revealed that the IR-Hi group maintained the diversity of TCR, and a portion of the IR-Hi cases held the T cells with shared TCR repertoires, implying recognition of shared antigens. The prognosis of patients with ESCC was affected by the existence of immune response cells and may possibly be stratified by the T-cell subsets.

Project description:BackgroundEsophageal microbiota may influence esophageal squamous cell carcinoma (ESCC) pathobiology. Therefore, we investigated the characteristics and interplay of the esophageal microbiota in ESCC.MethodsWe performed 16S ribosomal RNA sequencing on paired esophageal tumor and tumor-adjacent samples obtained from 120 primarily ESCC patients. Analyses were performed using quantitative insights into microbial 2 (QIIME2) and phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2). Species found to be associated with ESCC were validated using quantitative PCR.ResultsThe microbial diversity and composition of ESCC tumor tissues significantly differed from tumor-adjacent tissues; this variation between subjects beta diversity is mainly explained by regions and sampling seasons. A total of 56 taxa were detected with differential abundance between the two groups, such as R. mucilaginosa, P. endodontalis, N. subflava, H. Pylori, A. Parahaemolyticus, and A. Rhizosphaerae. Quantitative PCR confirmed the enrichment of the species P. endodontalis and the reduction of H. Pylori in tumor-adjacent tissues. Compared with tumor tissue, a denser and more complex association network was formed in tumor-adjacent tissue. The above differential taxa, such as H. Pylori, an unclassified species in the genera Sphingomonas, Haemophilus, Phyllobacterium, and Campylobacter, also participated in both co-occurrence networks but played quite different roles. Most of the differentially abundant taxa in tumor-adjacent tissues were negatively associated with the epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), erb-b2 receptor tyrosine kinase 4 (ERBB4), and fibroblast growth factor receptor 1 (FGFR1) signaling pathways, and positively associated with the MET proto-oncogene, receptor tyrosine kinase (MET) and phosphatase and tensin homolog (PTEN) signaling pathways in tumors.ConclusionAlterations in the microbial co-occurrence network and functional pathways in ESCC tissues may be involved in carcinogenesis and the maintenance of the local microenvironment for ESCC.

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Estrogen receptor ? and ? in esophageal squamous cell carcinoma.

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Estrogen receptor α and β in esophageal squamous cell carcinoma.

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