In:
Combinatorial Chemistry & High Throughput Screening, Bentham Science Publishers Ltd., Vol. 23, No. 5 ( 2020-07-09), p. 381-391
Abstract:
Tumor microenvironment (TME) cells play important roles in tumor
progression. Accumulating evidence show that they can be exploited to predict the clinical outcomes and therapeutic responses of tumor. However, the role of immune
genes of TME in small cell lung cancer (SCLC) is currently unknown. Objective: To determine the role of immune genes in SCLC. Methods: We downloaded the expression profile and clinical follow-up data of SCLC
patients from Gene Expression Omnibus (GEO), and TME infiltration profile data of 158 patients using CIBERSORT. The correlation between TME phenotypes, genomic
features, and clinicopathological features of SCLC was examined. A gene signature was constructed based on TME genes to further evaluate the relationship between
molecular subtypes of SCLC with the prognosis and clinical features. Results: We identified a group of genes that are highly associated with TME. Several
immune cells in TME cells were significantly correlated with SCLC prognosis (p 〈 0.0001). These immune cells displayed diverse immune patterns. Three molecular
subtypes of SCLC (TMEC1-3) were identified on the basis of enrichment of immune cell components, and these subtypes showed dissimilar prognosis profiles (p=0.03).
The subtype with the best prognosis, TMEC3, was enriched with immune activation factors such as oncogene M0, oncogene M2, T cells follicular helper, and T cells CD8
(p 〈 0.001). The TMEC1 subtype with the worst prognosis was enriched with T cells
CD4 naive, B cells memory and Dendritic cells activated cells (p 〈 0.001). Further
analysis showed that the TME was significantly enriched with immune checkpoint genes, immune genes, and immune pathway genes (p 〈 0.01). From the gene
expression data, we identified four TME-related genes, GZMB, HAVCR2, PRF1 and TBX2, which were significantly associated with poor prognosis in both the training
set and the validation set (p 〈 0.05). These genes may serve as markers for monitoring
tumor responses to immune checkpoint inhibitors. Conclusion: This study shows that TME features may serve as markers for evaluating
response of SCLC cells to immunotherapy.
Type of Medium:
Online Resource
ISSN:
1386-2073
DOI:
10.2174/1386207323666200407075004
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2020
SSG:
15,3
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