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Downregulation of FPN1 acts as a prognostic biomarker associated with immune infiltration in lung cancer.

ABSTRACT: Lung cancer morbidity and mortality remain the leading causes of tumor-associated death worldwide. The discovery of early diagnostic and prognostic markers of lung cancer could significantly improve the survival rate and decrease the mortality rate. FPN1 is the only known mammalian iron exporter. However, the molecular and biological functions of FPN1 in lung cancer remain unclear. Here, FPN1 mRNA expression in lung cancer was estimated using the TCGA, Oncomine, TIMER, and UALCAN databases. The prognostic role of FPN1 was evaluated using Kaplan-Meier plotter and PrognoScan. Associations between FPN1 and immune infiltration in lung cancer were evaluated by the TIMER and CIBERSORT algorithms. FPN1 mRNA and protein expressions were significantly downregulated in lung cancer. Low FPN1 expression was strongly related to worse prognosis in patients with lung cancer. GO and KEGG analyses and GSEA suggested that FPN1 was remarkably related to iron homeostasis and immunity. Importantly, FPN1 was remarkably associated with the infiltrating abundance of multiple immune cells. Moreover, FPN1 displayed a strong correlation with various immune marker sets. We investigated the clinical application value of FPN1 and provided a basis for the sensitive diagnosis, prognostication and targeted therapy of lung cancer.

SUBMITTER: Liu B

PROVIDER: S-EPMC8034901 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Downregulation of FPN1 acts as a prognostic biomarker associated with immune infiltration in lung cancer.

Liu Bing B Song Zhiyuan Z Fan Yumei Y Zhang Guangyu G Cao Pengxiu P Li Danyu D Liu Xiaopeng X Chang Yanzhong Y Tan Ke K

Aging 20210310 6

Lung cancer morbidity and mortality remain the leading causes of tumor-associated death worldwide. The discovery of early diagnostic and prognostic markers of lung cancer could significantly improve the survival rate and decrease the mortality rate. FPN1 is the only known mammalian iron exporter. However, the molecular and biological functions of FPN1 in lung cancer remain unclear. Here, FPN1 mRNA expression in lung cancer was estimated using the TCGA, Oncomine, TIMER, and UALCAN databases. The ...[more]

PMID: 33714956

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Project description:BackgroundZC3H12 family members have an important role in tumorigenesis and development. However, the relationship between ZC3H12 family members and the prognosis of lung adenocarcinoma (LUAD) and tumor infiltrating lymphocytes is not clear.MethodsThe expression of ZC3H12 family members in LUAD was analyzed by UALCAN. UALCAN, Kaplan-Meier Plotter, and GEPIA were used to evaluate the effect of ZC3H12 family members on the prognosis of LUAD. The relationship between prognostic ZC3H12 family members and 14 functional states of LUAD was studied by CancerSEA. The correlation between ZC3H12 and immune cell infiltration was studied by TIMMER. In addition, the correlation between ZC3H12D expression and an immune infiltration gene marker set was analyzed by TISIDB and GEPIA. Finally, the expression of ZC3H12D in LUAD was further verified by the GEO database and immunohistochemical staining.ResultsThe combined prognostic analysis of UALCAN, Kaplan-Meier Plotter, and GEPIA showed that the up-regulated expression of ZC3H12D mRNA was closely related to an improvement in overall survival rate (OS) in patients with LUAD. There was no significant correlation between ZC3H12D and 14 functional states of LUAD. Further analysis showed that the expression of ZC3H12D was positively correlated with the infiltration of B cells and CD4+T cells in LUAD. The expression of ZC3H12D was also positively correlated with immune markers in LUAD, including B cell-derived TNF and LTA cytokines, CXCL13, and its receptor CXCR5. Immunohistochemical staining showed that the expression of ZC3H12D in LUAD tissue samples was higher than normal lung tissues.ConclusionsThese findings suggest that multiple ZC3H12 family members are associated with the prognosis of patients with LUAD tumors. The increased expression of ZC3H12D was correlated with improved prognosis. ZC3H12D was shown to be associated with the level of immune cell infiltration, including B cells and CD4+T cells. Thus, ZC3H12D can be used as a biomarker to judge the prognosis and immune infiltration of LUAD.

Project description:BackgroundThe kinesin-13 family member 2C (KIF2C) is a versatile protein participating in many biological processes. KIF2C is frequently up-regulated in multiple types of cancer and is associated with cancer development. However, the role of KIF2C in immune cell infiltration of tumor microenvironment and immunotherapy in breast cancer remains unclear.MethodsThe expression of KIF2C was analyzed using Tumor Immune Estimation Resource (TIMER) database and further verified by immunohistochemical staining in human breast cancer tissues. The correlation between KIF2C expression and clinical parameters, the impact of KIF2C on clinical prognosis and independent prognostic factors were analyzed by using TCGA database, the Kaplan-Meier plotter, and Univariate and multivariate Cox analyses, respectively. The nomograms were constructed according to independent prognostic factors and validated with C-index, calibration curves, ROC curves, and decision curve analysis. A gene set enrichment analysis (GSEA) was performed to explore the underlying molecular mechanisms of KIF2C. The degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA (ssGSEA). The Tumor mutational burden and Tumor Immune Dysfunction and Rejection (TIDE) were used to analyze immunotherapeutic efficiency. Finally, the KIF2C-related competing endogenous RNA (ceRNA) network was constructed to predict the putative regulatory mechanisms of KIF2C.ResultsKIF2C was remarkably up-regulated in 18 different types of cancers, including breast cancer. Kaplan-Meier survival analysis showed that high KIF2C expression was associated with poor overall survival (OS). KIF2C expression was associated with clinical parameters such as age, TMN stage, T status, and molecular subtypes. We identified age, stage, estrogen receptor (ER) and KIF2C expression as OS-related independent prognosis factors for breast cancer. An OS-related nomogram was developed based on these independent prognosis factors and displayed good predicting ability for OS of breast cancer patients. Finally, our results revealed that KIF2C was significantly related to immune cell infiltration, tumor mutational burden, and immunotherapy in patients with breast cancer.ConclusionKIF2C was overexpressed in breast cancer and was positively correlated with immune cell infiltration and immunotherapy response. Therefore, KIF2C can serve as a potential biomarker for prognosis and immunotherapy in breast cancer.

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Downregulation of FPN1 acts as a prognostic biomarker associated with immune infiltration in lung cancer.

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Downregulation of FPN1 acts as a prognostic biomarker associated with immune infiltration in lung cancer.

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