Dataset Information

Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in Laryngeal Squamous Cell Carcinoma.

ABSTRACT: Laryngeal squamous cell carcinoma (LSCC) responds to 17?-estradiol via estrogen-receptor (ER, transcribed from ESR1) dependent mechanisms, but is not recognized as a hormonally responsive cancer. 17?-estradiol production by LSCC cell lines UM-SCC-11A and UM-SCC-12 was examined. Wild type (WT) and ESR1-silenced LSCC cultures and xenografts were examined for 17?-estradiol responsiveness in vivo. 14 LSCC and surrounding epithelial samples at various pathological stages were obtained from patients; ER? and ER? expression were verified using data from the total cancer genome atlas. UM-SCC-11A and UM-SCC-12 both produce 17?-estradiol, but only UM-SCC-12, not UM-SCC-11A, xenograft tumors grow larger in vivo in response to systemic 17?-estradiol treatments. ER?66 and ER?36 expression inversely correlated with clinical cancer stage and tumor burden. LSCC ER?66 expression was higher compared to surrounding epithelia in indolent samples but lower in aggressive LSCC. ER? expression was highly variable. High ESR1 expression correlated with improved survival in LSCC. Loss of ER?66 expression inversely correlated with prognosis in LSCC. ER?66 may be a histopathological marker of aggression in LSCC.

SUBMITTER: Verma A

PROVIDER: S-EPMC7060328 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in Laryngeal Squamous Cell Carcinoma.

Verma Anjali A Schwartz Nofrat N Cohen David J DJ Patel Vaidehi V Nageris Benny B Bachar Gideon G Boyan Barbara D BD Schwartz Zvi Z

Scientific reports 20200306 1

Laryngeal squamous cell carcinoma (LSCC) responds to 17β-estradiol via estrogen-receptor (ER, transcribed from ESR1) dependent mechanisms, but is not recognized as a hormonally responsive cancer. 17β-estradiol production by LSCC cell lines UM-SCC-11A and UM-SCC-12 was examined. Wild type (WT) and ESR1-silenced LSCC cultures and xenografts were examined for 17β-estradiol responsiveness in vivo. 14 LSCC and surrounding epithelial samples at various pathological stages were obtained from patients; ...[more]

PMID: 32144339

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Project description:ObjectiveThis study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC).MethodsThe mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively.ResultsThere were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC.ConclusionThis study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.

Dataset Information

Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in Laryngeal Squamous Cell Carcinoma.

Publications

Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in Laryngeal Squamous Cell Carcinoma.

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