Abstract

Objective To perform gene set enrichment analysis (GSEA) and analysis of immune cell infiltration on non-small-cell lung cancer (NSCLC) expression profiling microarray data based on bioinformatics, construct TICS scoring model to distinguish prognosis time, screen key genes and cancer-related pathways for NSCLC treatment, explore differential genes in NSCLC patients, predict potential therapeutic targets for NSCLC, and provide new directions for the treatment of NSCLC. Methods Transcriptome data of 81 NSCLC patients and the GEO database were used to download matching clinical data (access number: GSE120622). Form the expression of non-small cell lung cancer (NSCLC). TICS values were calculated and grouped according to TICS values, and we used mRNA expression profile data to perform GSEA in non-small-cell lung cancer patients. Biological process (GO) analysis and DAVID and KOBAS were used to undertake pathway enrichment (KEGG) analysis of differential genes. Use protein interaction (PPI) to analyze the database STRING, and construct a PPI network model of target interaction. Results We obtained 6 significantly related immune cells including activated B cells through the above analysis (Figure 1(b), p < 0.001). Based on the TICS values of significantly correlated immune cells, 41 high-risk and 40 low-risk samples were obtained. TICS values and immune score values were subjected to Pearson correlation coefficient calculation, and TICS and IMS values were found to be significantly correlated (Cor = 0.7952). Based on non-small-cell lung cancer mRNA expression profile data, a substantial change in mRNA was found between both the high TICS group as well as the low TICS group (FDR 0.01, FC > 2). The researchers discovered 730 mRNAs that were considerably upregulated in the high TICS group and 121 mRNAs that were considerably downregulated in the low TICS group. High confidence edges (combined score >0.7) were selected using STRING data; then, 191 mRNAs were matched to the reciprocal edges; finally, an undirected network including 164 points and 777 edges was constructed. Important members of cellular chemokine-mediated signaling pathways, such as CCL19, affect patient survival time. Conclusion (1) The longevity of patients with non-small-cell lung cancer was substantially connected with the presence of immature B cells, activated B cells, MDSC, effector memory CD4 T cells, eosinophils, and regulatory T cells. (2) Immune-related genes such as CX3CR1, CXCR4, CXCR5, and CCR7, which are associated with the survival of NSCLC, affect the prognosis of NSCLC patients by regulating the immune process.

Highlights

  • (1) e relative abundance of 28 immune cells of tumor infiltrating in 81 patients with non-small-cell lung cancer was quantified using single-sample gene set enrichment analysis. e prognosis of 28 immune cells was assessed using Cox risk regression analysis. e TICS value was calculated in terms of the risk value of immune cells and ssGSEA’s NES value, and the Z-score was calculated

  • We used mRNA expression data based on TICS group to conduct GSEA in patients with non-small-cell lung cancer (NSCLC). e results showed that the up-regulated genes affecting the prognosis of nonsmall cell lung cancer in the high TICS group were significantly related to the signal pathways of T cells and B cells (Figure 3(a)). is indicates that immune regulation is an important biological process affecting the prognosis of NSCLC, and the upregulated genes in the high TICS group are important molecules involved in its immune regulation

  • Relevant studies have shown that immune cells of adaptive immune and innate immune system can penetrate into tumor tissue, forming tumor immune microenvironment and affecting tumor progression

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Summary

Objective

To perform gene set enrichment analysis (GSEA) and analysis of immune cell infiltration on non-small-cell lung cancer (NSCLC) expression profiling microarray data based on bioinformatics, construct TICS scoring model to distinguish prognosis time, screen key genes and cancer-related pathways for NSCLC treatment, explore differential genes in NSCLC patients, predict potential therapeutic targets for NSCLC, and provide new directions for the treatment of NSCLC. TICS values were calculated and grouped according to TICS values, and we used mRNA expression profile data to perform GSEA in non-small-cell lung cancer patients. Based on non-small-cell lung cancer mRNA expression profile data, a substantial change in mRNA was found between both the high TICS group as well as the low TICS group (FDR 0.01, FC > 2). Only a few reports have investigated the clinic pathological significance of immune cells in recent years, and the overall expression level and prognostic value of immune cell infiltration, especially in NSCLC patients, require further investigation. erefore, in this study, we collected data from public databases and constructed statistical scoring models to analyze multiple datasets independently and pooled the analysis results in order to elucidate the prognosis-related molecular mechanisms of NSCLC, which helps to further understand the pathogenesis of NSCLC and provides new ideas and targets for the early diagnosis and treatment of NSCLC

Materials and Methods
1: Construction of Immune Microenvironment Map of NSCLC
Result
3: Related Genes of TICS Participate in Important Immune Pathways in NSCLC
4: Immune-Related Genes Are the Key to Distinguish TICS
C1QA CD27 CD40LG C1QB ITGB2 AGER
Findings
Discussion

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