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Gene & Protein in Disease                                              SCN7A is a protective factor in LUAD




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            Figure 3. Predictive nomogram showing the prognosis prediction potential of GRIA1, SCN7A, and CACNA2D2 for lung adenocarcinoma (LUAD).
            (A  and B) Univariate and multivariate regression analyses of the relationship between  GRIA1,  SCN7A, and  CACNA2D2 expression and LUAD
            prognosis.  (C and D) Nomogram of risk score and other clinical characteristics to predict the 1-year, 3-year, and 5-year overall survival (OS) of LUAD
            patients.

            proportion of stage II–IV cancers and a higher proportion   3.6. Immunological analysis of SCN7A in lung
            of survival (Figure  4A). These results link high SCN7A   adenocarcinoma
            expression with better survival outcomes.          The prognostic value of SCN7A for LUAD was evaluated. We
              Immunohistochemistry (IHC) analysis confirmed    first analyzed how SCN7A expression correlates to immune
            that SCN7A was moderately expressed in normal      cell infiltration to the tumor site based on the TIMER score.
            tissues  but was  entirely  absent  in  lung  cancer tissues   The results revealed a strong positive association between
            (Figure  4B). These results showed that mRNA and   SCN7A  expression  and  the  infiltration  of  six  immune
            protein levels of SCN7A are lower in LUAD tissues than   cell subtypes: B cells (r = 0.33, P = 8.1e-15) (Figure 6A),
                                                                   +
                                                                                                             +
            in normal tissues.                                 CD4  T cells (r = 0.34, P = 1.98e-15) (Figure 6B), CD8
                                                               T cells (r = 0.33, P = 2.05e-14) (Figure 6C), neutrophils
            3.5. Mutation studies of SCN7A in lung             (r  =  0.21,  P  =  2.04e-06) (Figure  6D), macrophages
            adenocarcinoma                                     (r = 0.42, P = 2.36e-23) (Figure 6E), and myeloid dendritic
            Since ion channels are involved in many cellular processes,   cell (r = 0.35, P = 2.99e-16) (Figure 6F). In addition, the
            mutations in related genes could cause a variety of   infiltration of the aforementioned immune cells was
                  [21]
            diseases . We screened for SCN7A mutations in LUAD   associated with favorable LUAD prognosis.
            genes based on the data in cBioPortal database.  SCN7A   We then analyzed the sCNA of SCN7A in pan-cancer
            mutations were detected in 6% of LUAD tissues, most of   using data in TIMER2.0 database (Figure 7A). We found
            which were missense mutations. A  total of 28 mutation   that the sCNA of SCN7A affects the infiltration of various
            sites and seven truncation mutations were identified in the   immune cells, including CD4  T cells, macrophages,
                                                                                         +
            genome of LUAD cells (Figure 5).                   neutrophils, and dendritic cells, in LUAD (Figure 7B).




            Volume 2 Issue 1 (2023)                         5                         https://doi.org/10.36922/gpd.363
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