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

advanced stage . Therefore, we need to understand the (MF), and DEGs-regulated pathways were identified from
[4]
molecular mechanism of how lung cancer develops and the Metascape database.
progresses to identify accurate markers for early diagnosis
and novel markers for treating the disease. 2.3. Expression and prognostic analysis
Ion channels are involved in many important biological Wilcox test was performed to analyze the prognostic
processes (BPs). The association between ion channels and value of SCN7A for LUAD. Based on the plotted Kaplan-
cancer development has been reported in many studies [5,6] . Meier (KM) survival curves, “survival” and “survminer”
LUAD cells display specific changes in the expression of packages in the R software were used to conduct the
ion channel-related genes. Since novel diagnostic markers survival analysis. The evaluation of the relationship
are urgently needed, these genes are promising clinical between SCN7A expression and LUAD prognosis was by
biomarkers for LUAD diagnosis and prognosis prediction. univariate Cox regression besides utilizing a forest plot to
In addition, the therapeutic potential of ion channel- display it graphically.
related genes for solid epithelial tumors and breast cancer 2.4. Genes related to overall survival in lung
have been reported [7-9] . However, we have not identified adenocarcinoma
any ion channel-related gene that could be targeted for
LUAD treatment. The genes significantly related to overall survival (OS)
in LUAD were identified by univariate and multivariate
In this study, differentially expressed genes (DEGs) analyses. Apart from SCN7A, the other parameters analyzed
related to ion channel between LUAD and normal for inclusion in a predictive nomogram included calcium
tissues were identified from LUAD datasets (GSE31552, voltage-gated channel auxiliary subunit alpha2delta 2
GSE33532, and GSE103512) in the Gene Expression (CACNA2D2) and glutamate ionotropic receptor AMPA
Omnibus (GEO) database [10-12] . SCN7A was identified to type subunit 1 (GRIA1), age, gender, and pathological
be significantly correlated to prognosis. The expression tumor-node-metastasis (pTNM) stage. A forest plot was
profile, mutational landscape, immunological role, and used to display the effect estimates of the aforementioned
prognostic value of SCN7A for LUAD were all analyzed. parameters on LUAD prognosis.
A competing endogenous RNA (ceRNA) network for
SCN7A was also constructed. We found that SCN7A 2.5. Messenger RNA transcription and protein level
influences the survival of LUAD patients, suggesting that expression analysis
SCN7A may be a protective factor in LUAD and can be
utilized to develop new therapeutic approaches. A Sankey diagram was constructed to visually demonstrate
the influence of age, gender, pTNM stage, and SCN7A
2. Materials and methods mRNA expression on LUAD prognosis. A map of protein
expression in 32 human tissues was taken from the Human
2.1. Data source and analysis Protein Atlas (HPA) database (http://www.proteinatlas.
[15]
The GEO database (https://www.ncbi.nlm.nih.gov/ org/) . SCN7A protein expression levels between lung
geo/) was used to download GSE31552, GSE33532, and cancer and normal tissues were analyzed in the HPA
GSE103512 datasets for the expression of LUAD genes , database. SCN7A expression in lung cancer tissues
[13]
which were then normalized using the quantiles function. (167201_B_1_1, 167201_B_1_2, and 167201_B_1_3)
DEGs were identified by “limma” R package based on and normal tissues (167203_A_1_4, 167203_A_2_4, and
P < 0.05 and |logFC| > 1. The “ggplot2” R package was 167203_A_3_4) was analyzed.
used to construct a volcano plot and heatmap. The genes
related to ion channels were identified from the Kyoto 2.6. Mutations in lung adenocarcinoma tissue cells
Encyclopedia of Genes and Genomes (KEGG) database cBioPortal (https://www.cbioportal.org/) contains five
(hsa04040), and The Cancer Genome Atlas (TCGA) published datasets and 15 provisional TCGA datasets and
database (https://tcga-data.nci.nih.gov/tcga/) was used for provides data for mutational analysis [16,17] .
downloading the TCGA pan-cancer RNA-seq data.
2.7. Immunological analysis
2.2. Gene ontology and Kyoto Encyclopedia of The correlation between immune score and LUAD
Genes and Genomes enrichment analyses prognosis was analyzed. TIMER2.0 (http://timer.cistrome.

The Metascape platform integrates gene annotation, org/) contains data on immune cell infiltration to cancer
enrichment analysis, and interactome analysis by tissues . The impact of somatic copy number alteration
[18]
leveraging 40 independent gene expression databases . (sCNA) of SCN7A on immune infiltration was analyzed
[14]
The BP, cellular component (CC), molecular function using TIMER2.0 data.

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