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SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer.

ABSTRACT: The zinc transporter SLC39A4 influences epithelial cell morphology and migration in various cancers; however, its role in regulating cell invasion and chemotherapeutic resistance in human lung cancer is not yet clear. Here, integrated analysis of gene expression in non-small cell lung cancer revealed that SLC39A4 expression is significantly correlated with increased tumour size and regional lymph node spread, as well as shorter overall survival (OS) and disease-free survival (DFS). SLC39A4 silencing by lentivirus-mediated shRNA blocked human lung cancer cell epithelial-mesenchymal transition and metastasis in vitro and in vivo, respectively. Moreover, SLC39A4 knockdown enhanced cancer cell sensitivity to cisplatin-induced death by inhibiting stemness in lung cancer cells. Collectively, these data suggest that SLC39A4 may be a novel therapeutic target and predictive marker of tumour metastasis in non-small cell lung cancer.

SUBMITTER: Wu DM

PROVIDER: S-EPMC5543149 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer.

Wu Dong-Ming DM Liu Teng T Deng Shi-Hua SH Han Rong R Xu Ying Y

Scientific reports 20170803 1

The zinc transporter SLC39A4 influences epithelial cell morphology and migration in various cancers; however, its role in regulating cell invasion and chemotherapeutic resistance in human lung cancer is not yet clear. Here, integrated analysis of gene expression in non-small cell lung cancer revealed that SLC39A4 expression is significantly correlated with increased tumour size and regional lymph node spread, as well as shorter overall survival (OS) and disease-free survival (DFS). SLC39A4 silen ...[more]

PMID: 28775359

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Project description:Background: Cisplatin is the basis of the primary treatment for SCLC chemotherapy. However, the limited objective response rate and definite drug resistance greatly restrict the clinical potential and therapeutic benefits of cisplatin use. Therefore, it is essential to identify biomarkers that can discern the sensitivity of SCLC patients to cisplatin treatment. Methods: We collected two SCLC cohorts treated with cisplatin that included mutation data, prognosis data and expression data. The sensitivity of cisplatin was evaluated by the pRRophetic algorithm. MCPcounter, quanTIseq, and xCell algorithms were used to evaluate immune cell score. GSEA and ssGSEA algorithms were used to calculate immune-related pathway scores. Univariate and multivariate Cox regression models were employed, and survival analysis was used to evaluate the prognostic value of the candidate genes. Results: MMP9-High is related to improved clinical prognoses of patients with SCLC (HR = 0.425, p = 0.0085; HR = 0.365, p = 0.0219). Multivariate results showed that MMP-High could be used as an independent predictor of the prognosis of SCLC after cisplatin treatment (HR = 0.216, p = 0.00153; HR = 0.352; p = 0.0199). In addition, MMP9-High displayed a significantly lower IC50 value of cisplatin and higher immunogenicity than MMP9-Low SCLC. Compared with MMP9-Low SCLC, MMP9-High included significantly increased levels of T-cells, cytoxic lymphocytes, B-cells, NK-cells, and dense cells (DCS). Similarly, the activity of cytokine binding, B-cell, NK-cell mediated immune response chemokine binding, and antigen presentation pathways in MMP9-High was significantly higher than that in MMP9-Low. Conclusion: In this study, we identified that MMP9-High could be potentially considered a novel biomarker used to ascertain the improved prognosis of SCLC patients after cisplatin treatment. Furthermore, we indicated that the tumor immune microenvironment of MMP9-High SCLC is mainly characterized by a large number of infiltrated activated immune cells as well as activated immune-related pathways.

Dataset Information

SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer.

Publications

SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer.

Similar Datasets

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