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Gene & Protein in Disease                                           Significance of MXRA7 in bladder cancer



            exosome”, “calcium ion binding”, etc. Together this,   3.3. Differential survival curves of BLCA patients
            evidence suggests that MXRA7 may promote the survival,   correlated with MXRA7 expression levels
            proliferation, invasion, and  migration  of BLCA cells   When KM survival curves were obtained with log-rank
            through  regulation of  cytoskeleton or  interaction with   analysis on BLCA patients with varying levels of MXRA7,
            extracellular matrix.
                                                               it was noted that high MXRA7 expression was associated
                                                               with a significantly unfavorable prognosis for PFS
            A
                                                               (Figure 3A). This indicates that patients with high MXRA7
                                                               levels are more likely to experience disease worsening or
                                                               relapse, suggesting that MXRA7 may serve as a biomarker
                                                               for predicting disease progression and treatment resistance
                                                               rather than recurrence risk. In contrast, no significant
                                                               correlation was found between  MXRA7 expression and
                                                               DFI (Figure 3B), implying that MXRA7 expression does
                                                               not strongly influence post-treatment recurrence rates in
                                                               patients who have achieved complete remission.
                                                               3.4. LASSO regression analysis of DEGs
            B
                                                               After conducting a LASSO regression analysis by
                                                               integrating patients’ survival data and gene expression
                                                               levels (Limma) (as detailed in the Methods section),
                                                               15 genes were identified (Figure 4A), with the optimal λ
                                                               approximately at 0.05 (Figure  4B), indicating the lowest
                                                               model error. The heatmap showed that the expression levels
                                                               of protective genes like UPK2 decreased with risk, whereas
                                                               the expression levels of risk factors like MFAP5 increased
                                                               (Figure  4C).  Furthermore,  as  the  risk  score  increased,
                                                               the number of patient deaths increased significantly.
                                                               A downstream analysis of 15 genes was then performed to
            Figure  2.  Functional  enrichment  analysis  of  MXRA7-associated  genes   further evaluate the prognostic significance of each gene in
            highlighting key pathways in BLCA progression and invasiveness. (A) The   325 clinical samples. The overall prognosis difference was
            KEGG crucial pathways are represented on a bar chart, with gene counts   significant, with key statistics including (logtest = 3.15e-08,
            on the horizontal axis, pathway names on the vertical axis, and p-values
            indicated by color. (B) The enriched GO terms (MF, CC, BP) were   sctest = 4.28e-10, waldtest = 3.85e-09), and C-index was
            depicted on a bubble diagram, with fold enrichment on the horizontal   0.65. The six significant genes identified were RRAD, UPK2,
            axis, pathway names on the vertical axis, point size representing gene   PDPN, PDLIM4, SRPX, and MYLK (Figure 4D). The risk
            counts, and p-values in -log10 indicated by color.  score for BLCA patients hence could be calculated using
            Abbreviations: BLCA: Bladder cancer; MF: Molecular function;
            CC:  Cellular component; BP: Biological process; KEGG: Kyoto   the formula: risk score = 0.009997*SRPX-0.032084*MYLK-
            Encyclopedia of Genes and Genomes; GO: Gene ontology.  0.023840*PDPN+0.003429*PXDN-0.062056*RRAD-

                         A                                  B














            Figure 3. Kaplan–Meier survival analysis indicating high MXRA7 expression as a prognostic risk factor for PFS in BLCA. (A) Comparison of the PFS
            survival curves of BLCA patients based on MXRA7 expression levels. (B) DFI analysis in relation to MXRA7 expression in BLCA conditions.
            Abbreviations: BLCA: Bladder cancer; PFS: Progression-free survival; DFI: Disease-free interval.

            Volume 4 Issue 2 (2025)                         5                               doi: 10.36922/gpd.6256
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