Dataset Information

SLC39A4 as a Novel Prognosis Marker Promotes Tumor Progression in Esophageal Squamous Cell Carcinoma.

ABSTRACT: Background:Solute carrier family 39 member 4 (SLC39A4) has been reported to play an oncogenic role in several cancers. However, the role of SLC39A4 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to explore the clinical significance and function of SLC39A4 in ESCC. Methods:The Cancer Genome Atlas and Gene Expression Omnibus databases were analyzed to assess the level of SLC39A4 in ESCC. The expression level of SLC39A4 was measured by RT-qPCR and immunohistochemistry in a cohort of 73 patients aged 45-65 years with ESCC. Kaplan-Meier analysis was used to identify the correlation between SLC39A4 and the prognosis of ESCC patients. In vitro experiments were conducted to explore the biological function of SLC39A4 in ESCC cell line TE-1 and TE-10. Results:The mRNA level of SLC39A4 was significantly enhanced in ESCC specimens, which was in line with the outcome of online databases analysis. Moreover, the aberrant expression of SLC39A4 was positively correlated with clinical stage, T categories and lymph node metastasis. Kaplan-Meier analysis indicated that elevated SLC39A4 expression predicted poor prognosis of patients with ESCC. Furthermore, the in vitro experiments showed that SLC39A4 knockdown not only impaired the proliferation and motility capacities of ESCC cells but also enhanced the sensitivity to cisplatin treatment. Conclusion:Our findings suggest that SLC39A4 could serve as a novel prognosis biomarker to promote ESCC progression?; however, the mechanism of SLC39A4 in ESCC remains to be further explored.

SUBMITTER: Xia C

PROVIDER: S-EPMC7227820 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SLC39A4 as a Novel Prognosis Marker Promotes Tumor Progression in Esophageal Squamous Cell Carcinoma.

Xia Chenmei C Chen Xia X Li Jun J Chen Peng P

OncoTargets and therapy 20200511

<h4>Background</h4>Solute carrier family 39 member 4 (SLC39A4) has been reported to play an oncogenic role in several cancers. However, the role of SLC39A4 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to explore the clinical significance and function of SLC39A4 in ESCC.<h4>Methods</h4>The Cancer Genome Atlas and Gene Expression Omnibus databases were analyzed to assess the level of SLC39A4 in ESCC. The expression level of SLC39A4 was measured by RT-qPCR a ...[more]

PMID: 32494154

Similar Datasets

Project description:Objective: The transcription factor forkhead box protein O1 (FOXO1) is critical for regulating cytokine and chemokine secretion. However, its function in the tumor microenvironment (TME) remains largely unexplored. In this study, we characterized the prognostic value of FOXO1 and the interaction between tumor-derived FOXO1 and M2 macrophages in esophageal squamous cell carcinoma (ESCC). Methods: FOXO1 expression and macrophage infiltration in clinical samples and mouse models were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry staining. Western blotting, qRT-PCR, and enzyme-linked immunosorbent assay were used to evaluate chemokine ligand 20 (CCL20) and colony stimulating factor 1 (CSF-1) expression in FOXO1(+) and FOXO1(-) tumor cells. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and RNA sequencing. Transcriptional activity was measured using chromatin immunoprecipitation (ChIP)-qPCR. Tumor viability was investigated using XTT proliferation and foci formation assays. Results: FOXO1 upregulation in tumor tissues was found to drive the polarization of M0 macrophages and infiltration of M2 macrophages into the TME, resulting in worse prognosis in ESCC patients. CSF-1, a vital factor inducing M0-to-M2 polarization, was upregulated via a FOXO1-mediated mechanism. RNA sequencing results corroborated that the FOXO1-induced macrophages exhibited similar molecular signatures to the IL4-stimulated M2 macrophages. The transwell assays showed that FOXO1 promoted the migration of M2 macrophages via CCL20 secretion, which could be inhibited using an anti-CCL20 antibody. FOXO1(+) tumor-induced M2 macrophages promoted tumor proliferation via the FAK-PI3K-AKT pathway and the PI3K inhibitor could effectively impede the oncogenical process. Conclusions: FOXO1 facilitated M0-to-M2 polarization and the recruitment of M2 macrophages in the TME via the transcriptional modulation of CCL20 and CSF-1. Our data deciphered the FOXO1-dependent mechanism in M2 macrophage infiltration in the TME of ESCC, which has implications for the development of novel prognostic and therapeutic targets to optimize the current treatment against ESCC.

Dataset Information

SLC39A4 as a Novel Prognosis Marker Promotes Tumor Progression in Esophageal Squamous Cell Carcinoma.

Publications

SLC39A4 as a Novel Prognosis Marker Promotes Tumor Progression in Esophageal Squamous Cell Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets