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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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                       14 
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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
                                               20
            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
                           21
            malignancy among men,  accounting for about        the “lmFit” function for multiple linear regression and
                                   22
            5%  in  metastatic  diseases.   While  therapies  such  as   the “eBayes” function for empirical Bayes moderation of
                                   23
            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
                  20
            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
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