Dataset Information

Bioinformatics-Based Discovery of CKLF-Like MARVEL Transmembrane Member 5 as a Novel Biomarker for Breast Cancer.

ABSTRACT: Chemokine-like factor (CKLF)-like MARVEL transmembrane members (CMTMs) represent a novel protein family linking the chemokine and transmembrane-4 superfamily families, which potentially play several roles in diverse physiological and pathological processes. The detailed functions and underlying molecular mechanisms of CMTMs remain elusive in breast cancer. Herein, we performed a comprehensive bioinformatic analysis to investigate the prognostic effect, potential functions, and biomolecular regulatory network of CMTMs in breast cancer. The mRNA expression level of CMTM5, in particular, was significantly downregulated in breast cancer; moreover, high mRNA expression level of CMTM5 was significantly associated with better relapse-free survival. DNA promoter hypermethylation of CMTM5 was negatively correlated with its mRNA expression levels. Furthermore, CMTM5 strongly associated with pathway in MARVEL domains, chemotaxis, cytokines, transmembrane structures, and integral component of membrane. For example, genes related to MARVEL domains, transmembrane structures, and chemokines were significantly enriched. Our findings indicate that CMTM5 can be used as a prognostic biomarker and potential therapeutic target for breast cancer.

SUBMITTER: Zhou J

PROVIDER: S-EPMC6962189 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Bioinformatics-Based Discovery of CKLF-Like MARVEL Transmembrane Member 5 as a Novel Biomarker for Breast Cancer.

Zhou Juan J Lei Jian J Wang Jun J Lian Chen-Lu CL Hua Li L He Zhen-Yu ZY Wu San-Gang SG

Frontiers in cell and developmental biology 20200109

Chemokine-like factor (CKLF)-like MARVEL transmembrane members (CMTMs) represent a novel protein family linking the chemokine and transmembrane-4 superfamily families, which potentially play several roles in diverse physiological and pathological processes. The detailed functions and underlying molecular mechanisms of CMTMs remain elusive in breast cancer. Herein, we performed a comprehensive bioinformatic analysis to investigate the prognostic effect, potential functions, a ...[more]

PMID: 31998718

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Project description:BackgroundDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the world. Emerging evidence has shown that urinary mRNAs may serve as early diagnostic and prognostic biomarkers of DKD. In this article, we aimed to first establish a novel bioinformatics-based methodology for analyzing the "urinary kidney-specific mRNAs" and verify their potential clinical utility in DKD.MethodsTo select candidate mRNAs, a total of 127 Affymetrix microarray datasets of diabetic kidney tissues and other tissues from humans were compiled and analyzed using an integrative bioinformatics approach. Then, the urinary expression of candidate mRNAs in stage 1 study (n?=?82) was verified, and the one with best performance moved on to stage 2 study (n?=?80) for validation. To avoid potential detection bias, a one-step Taqman PCR assay was developed for quantification of the interested mRNA in stage 2 study. Lastly, the in situ expression of the selected mRNA was further confirmed using fluorescent in situ hybridization (FISH) assay and bioinformatics analysis.ResultsOur bioinformatics analysis identified sixteen mRNAs as candidates, of which urinary BBOX1 (uBBOX1) levels were significantly upregulated in the urine of patients with DKD. The expression of uBBOX1 was also increased in normoalbuminuric diabetes subjects, while remained unchanged in patients with urinary tract infection or bladder cancer. Besides, uBBOX1 levels correlated with glycemic control, albuminuria and urinary tubular injury marker levels. Similar results were obtained in stage 2 study. FISH assay further demonstrated that BBOX1 mRNA was predominantly located in renal tubular epithelial cells, while its expression in podocytes and urothelium was weak. Further bioinformatics analysis also suggested that tubular BBOX1 mRNA expression was quite stable in various types of kidney diseases.ConclusionsOur study provided a novel methodology to identify and analyze urinary kidney-specific mRNAs. uBBOX1 might serve as a promising biomarker of DKD. The performance of the selected urinary mRNAs in monitoring disease progression needs further validation.

Project description:BackgroundTamoxifen is the first-line hormone therapy for estrogen receptor alpha positive (ERα+) breast cancer. However, about 40% of patients with ERα + breast cancer who receive tamoxifen therapy eventually develop resistance resulting in a poor prognosis. The aim of this study was to mine available data sets in the Gene Expression Omnibus (GEO) database, including in vitro (cell lines) and in vivo (tissue samples), and to identify all miRNAs associated with tamoxifen resistance (TamR) in breast cancer. Secondly, this study aimed to predict the key gene regulatory networks of newly found TamR-related miRNAs and evaluate the potential role of the miRNAs and targets as potential prognosis biomarkers for breast cancer patients.ResultMicroarray data sets from two different studies were used from the GEO database: 1. GSE66607: miRNA of MCF-7 TamR cells; 2. GSE37405: TamR tissues. Differentially expressed microRNAs (miRNAs) were identified in both data sets and 5 differentially expressed miRNAs were found to overlap between the two data sets. Profiles of GSE37405 and data from the Kaplan-Meier Plotter Database (KMPD) along with Gene Expression Profiling Interactive Analysis (GEPIA) were used to reveal the relationship between these 5 miRNAs and overall survival. The results showed that has-miR-542-5p was the only miRNA associated with overall survival of ERα + breast cancer patients who received adjuvant tamoxifen. Targets of has-miR-542-5p were predicted by miRanda and TargetScan, and the mRNA expression of the three 3 target gene, Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Beta (YWHAB), Lymphocyte Antigen 9 (LY9), and Secreted Frizzled Related Protein 1 (SFRP1) were associated with overall survival in 2 different databases. Copy-number alterations (CNAs) of SFRP1 confer survival disadvantage to breast cancer patients and alter the mRNA expression of SFRP1 in cBioPortal database.ConclusionThis study indicates that miRNA has-miR-542-5p is associated with TamR and can predict prognosis of breast cancer patients. Furthermore, has-miR-542-5p may be acting through a mechanism involving the target genes YWHAB, LY9, and SFRP1. Overall, has-miR-542-5p is a predictive biomarker and potential target for therapy of breast cancer patients.

Dataset Information

Bioinformatics-Based Discovery of CKLF-Like MARVEL Transmembrane Member 5 as a Novel Biomarker for Breast Cancer.

Publications

Bioinformatics-Based Discovery of <i>CKLF</i>-Like <i>MARVEL</i> Transmembrane Member 5 as a Novel Biomarker for Breast Cancer.

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