Dataset Information

Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes.

ABSTRACT: Myelodysplastic syndrome is one of the main hematological malignancies that threaten the health of the elderly. However, biomarkers which predict the progression and prognosis of MDS are still controversial and puzzling. FOXO1 gene plays an important role in a variety of intracellular functions, including tumor suppression and cellular immune regulation. However, there is no research report on the correlation between FOXO1 and the clinical features of MDS including immune environment. In this study, we observed that FOXO1 expression is associated with neutrophil count, blasts, chromosome and different MDS scoring systems. FOXO1 expression is closely related to MDS cell immune polarization, and the increase expression of FOXO1 is significantly related to the amplification of immune cell polarization ratio. In addition, FOXO1 expression is associated with progression-free survival and overall survival in MDS patients. Moreover, in a multivariate model FOXO1 low-expression was an independent predictor of poor survival in MDS. In summary, FOXO1 may play a candidate tumor suppressor in MDS, and FOXO1 is a useful independent prognostic predictor in MDS, and it may provide a candidate target therapy in future.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC9600488 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes.

Zhang Zheng Z Huang Nanfang N Xv Feng F Zhao Sida S Guo Juan J Zhao Youshan Y Chang Chunkang C

Current oncology (Toronto, Ont.) 20220925 10

Myelodysplastic syndrome is one of the main hematological malignancies that threaten the health of the elderly. However, biomarkers which predict the progression and prognosis of MDS are still controversial and puzzling. FOXO1 gene plays an important role in a variety of intracellular functions, including tumor suppression and cellular immune regulation. However, there is no research report on the correlation between FOXO1 and the clinical features of MDS including immune environment. In this st ...[more]

PMID: 36290822

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Project description:BackgroundInositol Polyphosphate-5-Phosphatase B (INPP5B), a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD.MethodsTCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein-protein interactions. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays.ResultINPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway.ConclusionOur results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People's Hospital. The Ethics Committee of Hangzhou First People's Hospital has approved this study. (registration number: IIT-20210907-0031-01; registration date: 2021.09.13).

Dataset Information

Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes.

Publications

Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes.

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