SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas
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Cancer Cell International Open Access
PRIMARY RESEARCH
SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas Peng Wang1†, Jingjing Zhang1†, Shuai He2, Boan Xiao1 and Xiaobin Peng1*
Abstract Background: Gliomas are one of the most common primary tumors of the central nervous system, and have an unfavorable prognosis. SLC39A1 is a zinc ion transport protein which inhibits the progression of prostate cancer. By studying the role and mechanism of SLC39A1 in the progression of gliomas, perhaps a new therapeutic target can be provided for their treatment. Method: The TCGA, CCGA, GSE16011, GSE44971 and GSE11260 data sets were employed to evaluate the expression level of SLC39A1 in paracancerous and glioma tissues. In addition, Kaplan–Meier analysis, Cox analysis, and the ESTIMATE and CIBERSORT algorithms were used to analyze its prognostic value and immune infiltration correlation. A CCK-8 and flow cytometer were used to measure the effects of SLC39A1 on U87 cell proliferation or apoptosis; RTqPCR and western blot were used to detect its effects on the expression of MMP2\MMP9. Results: SLC39A1 has up-regulated expression in glioma tissues. High SLC39A1 expression predicted significantly worse survival. Univariate and multivariate analysis show that SLC39A1 independently indicated poor prognosis in patients with gliomas. The expression of SLC39A1 is significantly correlated with clinical pathological parameters such as Grade, IDH mutation status, and 1p19q codeletion status. In vitro experimental results show that SLC39A1 promotes proliferation of glioma cells, inhibits their apoptosis, and promotes expression of MMP2\MMP9. In addition, it may affect infiltration of immune cells into the glioma microenvironment. Conclusion: SLC39A1 may serve as a new prognostic biomarker and potential target for treatment of gliomas. Keywords: Glioma, SLC39A1, Malignant progression, Clinical prognostic impact, MMP2\MMP9, Immune infiltration Background Gliomas are one of the most common and aggressive primary tumors in the central nervous system (CNS). Their incidence accounts for 40% to 50% of the total incidence of intracranial tumors. They are highly malignant and result in a short survival time. In particular, the median survival time for patients suffering from glioblastoma *Correspondence: [email protected] † Peng Wang and Jingjing Zhang should be regarded as joint first authors 1 The Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China Full list of author information is available at the end of the article
multiforme (GBM), one of the most well-known malignant tumors in humans [1–3], is only 12-15 months. The average one-year survival rate is about 46%, while the 5-year survival rate is only 3%. The main clinical treatments for gliomas are currently surgery, radiotherapy and chemotherapy, but they usually fail to achieve the desired results, and the clinical prognosis is extremely poor [4, 5]. Therefore, further research on the occurrence and development of
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