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Gene & Protein in Disease Significance of MXRA7 in bladder cancer
(both adenoma-carcinoma transition and non-metastatic nomogram was employed to evaluate the reliability of
cases), 11,12 breast cancer basal stem cells, inflammatory MXRA7 as a biomarker for BLCA prognosis.
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breast cancer, male hepatocellular carcinoma, HPV-
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negative oropharyngeal carcinoma, and malignant 2. Methods
peripheral schwannoma. In contrast, some research 2.1. BLCA transcriptome profiling and Limma
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showed down-regulation of MXRA7 in retinoblastoma. differential analysis
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In addition, analysis of the Human Protein Atlas from
the Cancer Genome Atlas data suggested that higher Raw data for BLCA RNA-seq datasets were obtained
MXRA7 expression was associated with poor prognosis from TCGA (https://portal.gdc.cancer.gov/). The v22 and
v33 gff3 files were downloaded from GENCODE to map
in urothelial carcinoma. Up-regulated MXRA7 gene GeneSymbols to ENSG_IDs. In case multiple matches
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levels were disclosed in high-risk patients with bladder occurred, the median expression value was used to
cancer (BLCA) through differential analysis. While these generate the transformed expression profile. The median
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findings hint at a significant correlation between MXRA7 MXRA7 expression level was used to divide the BLCA
expression and certain cancers, comprehensive studies clinical samples into high expression (MXRA7-H) and
explicitly addressing MXRA7’s biological significance low expression (MXRA7-L) groups. When a gene symbol
in malignancies have been limited, apart from research corresponded to multiple gene IDs, the median value
conducted by our team. The current study aimed to fill was taken for generating standardized gene expression
7-9
this gap by specifically analyzing MXRA7’s role in BLCA data. Differential analysis was conducted using the R
progression and prognosis. package “Limma” to identify DEGs in MXRA7-H verse
As a leading cause of death, cancer poses a significant MXRA7-L, with fold changes of 2.0 as threshold to
threat to human health and places a substantial financial determine the “differential” between these two groups.
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burden on society. BLCA is the fourth most common Expression profiles were log2 transformed, followed by
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malignancy among men, accounting for about the “lmFit” function for multiple linear regression and
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5% in metastatic diseases. While therapies such as the “eBayes” function for empirical Bayes moderation of
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immunotherapy and targeted treatments are emerging, standard errors. This approach facilitated the calculation
accurately predicting the survival of BLCA patients of moderated t-statistics, moderated F-statistic, and log-
remains a challenge for healthcare providers and a focus odds of differential expression, culminating in significance
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of research. Since MXRA7 has been suspected to be assessment of gene expression differences. The results
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correlated with tumor progression or metastasis in some were exhibited using heat map and volcano plot to clearly
cancers, defining the role of MXRA7 in cancers might visualize the differences in gene expression between the
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provide insights into patient prognosis and support high and low-expression groups.
more personalized treatment strategies. Therefore, it is 2.2. Pathways enrichment and functional annotation
of significance to examine and solidify the behavior of analysis
MXRA7 in cancers, including BLCA.
Based on MXRA7 expression in the transcriptomic
A pan-cancer bioinformatic analysis by our team datasets derived from BLCAs, a total of 230 genes were
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(submitted for publication) and others suggested that up-regulated and 63 were down-regulated, and they were
MXRA7 manifested differential alterations in various used for additional functional enrichment analysis. DAVID
cancers. The current study was performed to further analyze bioinformatics in combination with Knowledgebase
the role of MXRA7 in the prognosis of BLCA through v2024q2 (released on July 5, 2024) was used to identify
expression profiling and linear models for microarray data significant Kyoto Encyclopedia of Genes and Genomes
(Limma) analysis. Differentially expressed genes (DEGs) (KEGG) pathways and GO terms. 28,29 DEGs were selected
retrieved on the basis of MXRA7 expression difference were based on a |log2 fold change| > 1.0 and an adjusted p-value
subjected to the database for annotation, visualization, and (false discovery rate [FDR]) <0.05. Pathways with an FDR
integrated discovery (DAVID) enrichment assay to uncover <0.05 were considered significant. KEGG pathway analysis
potential pathways or gene ontology (GO) terms associated was specifically performed to investigate the involvement
with the functions of MXRA7 in BLCA. A least absolute of these DEGs in cellular processes, focusing on pathways
shrinkage and selection operator (LASSO) model was and GO terms potentially relevant to tumorigenesis and
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then established to categorize the patients into “high-risk” cancer progression. The enriched pathways and functional
and “low-risk” groups. Subsequently, multivariate Cox terms were further analyzed to identify key biological
regression analysis was utilized to identify the significant processes and signaling pathways that might play a role in
factors for the prognostic model in clinical data. Finally, the biology of BLCA.
Volume 4 Issue 2 (2025) 2 doi: 10.36922/gpd.6256

