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Abstract
Objectives: Sm proteins (SNRPB/D1/D2/D3/E/F/G), involved in pre-mRNA splicing, were previously reported in the tumorigenesis of several cancers. However, their specific role in lung adenocarcinoma (LUAD) remains obscure. Our study aims to feature abnormal expressions and mutations of genes for Sm proteins and assess their potential as therapeutic targets via integrated bioinformatics analysis. Methods: In this research, we explored the expression pattern and prognostic worth of genes for Sm proteins in LUAD across TCGA, GEO, UALCAN, Oncomine, Metascape, David 6.8, and Kaplan-Meier Plotter, and confirmed its independent prognostic value via univariate and multivariate cox regression analysis. Meanwhile, their expression patterns were validated by RT-qPCR. Gene mutations and co-expression of genes for Sm proteins were analyzed by the cBioPortal database. The PPI network for Sm proteins in LUAD was visualized by the STRING and Cytoscape. The correlations between genes for Sm proteins and immune infiltration were analyzed by using the “GSVA” R package. Results: Sm proteins genes were found upregulated expression in both LUAD tissues and LUAD cell lines. Moreover, highly expressed mRNA levels for Sm proteins were strongly associated with short survival time in LUAD. Genes for Sm proteins were positively connected with the infiltration of Th2 cells, but negatively connected with the infiltration of mast cells, Th1 cells, and NK cells. Importantly, Cox regression analysis showed that high SNRPD1/E/F/G expression were independent risk factors for the overall survival of LUAD. Conclusion: Our study showed that SNRPD1/E/F/G could independently predict the prognostic outcome of LUAD and was correlated with immune infiltration. Also, this report laid the foundation for additional exploration on the potential treatment target’s role of SNRPD1/E/F/G in LUAD.
Highlights
Lung cancer is the most well-known sort of malignant tumor worldwide and is the major cause of cancer mortality (Sung et al, 2021)
We explored if the dyregulation of genes for Sm proteins had any impacts on the overall survival (OS) of Lung adenocarcinoma (LUAD) patients with smoke history by using the Kaplan Meier plotter
We investigated dendritic cell (DC), activated dendritic cell, immature dendritic cell,plasmacytoid dendritic cell, B cells, CD8+ T cells, Cytotoxic T cells, T cells, T helper cells, T help 1 (Th1) cells, Th17 cells, Th2 cells, T central memory (Tcm), T effector memory (Tem), T follicular helper (Tfh), T gamma delta (Tgd), regulatory T Cell (Treg), eosinophils, macrophages, mast cells, neutrophils, natural killer (NK) cells, NK CD56bright cells and NK CD56dim cells (Bindea et al, 2013), and the above associations was performed using single-sample Gene Sets Enrichment Analysis algorithm of R package “GSVA” (Hanzelmann et al, 2013) and lollipop charts were produced using R package “ggplot2.”
Summary
Lung cancer is the most well-known sort of malignant tumor worldwide and is the major cause of cancer mortality (Sung et al, 2021). Lung adenocarcinoma (LUAD) has been the most common subtype of Non-small cell cancer (NSCLC) (Anonymous, 2015). LUAD is characterized by a lack of early clinical symptoms, a high rate of distant metastasis and drug resistance, which pose serious challenges to clinical treatment. Treatment methods for LUAD mainly include surgical resection, radiotherapy, chemotherapy, immunotherapy, and molecular targeted therapy (Reck and Rabe, 2017). The best treatment for lung cancer is surgical resection in the early stages of lung cancer. The treatment of advanced lung adenocarcinoma is limited, and molecular targeted therapy is a promising choice, as well as immunotherapy. Because of the lack of effective molecular targets, most drugs remain ineffective in the treatment of LUAD patients, of whom the 5-year survival rate is just 15% (Chen et al, 2016). It is absolutely necessary to recognize effective and dependable biomarkers to determine poor prognoses and direct treatment strategies
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