CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma

Abstract

BackgroundThe tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD).MethodsThe gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein–protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues.ResultsWe identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan–Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis.ConclusionCSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies.

The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer

“…GM-CSF has been controversially related to both pro-cancer and anti-cancer functions, but its utilization as an immune adjuvant in cancer immunotherapy clinical trials [72] suggests that it can enhance antitumor efficacy. Higher CSF2RB expression in lung adenocarcinoma tumors is associated with better survival [73], in line with our observations in peripheral blood. Lastly, Interferon-Induced Transmembrane Protein 2 (IFITM2) is a member of a protein family which inhibits viral entry into host cells [74].…”

Identification of a novel survival predictor, CSF2RB, for female lung cancer in never smokers (LCNS) by a bioinformatics analysis

“…[15] Besides, CSF2RB was identified as important in the tumor microenvironment of lung adenocarcinoma (LUAD). [20] In our study, the module analysis of the PPI network presented that the progression of female LCNS was significantly associated with immune response as chemokine activity and lipopolysaccharide response, and these BP might be mediated by chemokine signaling pathway and cytokine-cytokine receptor interaction. Although recent bioinformatics studies have aimed to investigate hub genes for lung cancer and have reported that CSF2RB might be a survival-related gene of LUAD, [11,13] limited research has been focused on "female" nonsmokers with lung cancer cohorts.…”

“…[15] Besides, CSF2RB was identified as important in the tumor microenvironment of lung adenocarcinoma (LUAD). [20] In our study, the module analysis of the PPI network presented that the progression of female LCNS was significantly associated with immune response as chemokine activity and lipopolysaccharide response, and these BP might be mediated by chemokine signaling pathway and cytokine-cytokine receptor interaction.…”

Transcriptional profiles of functionally distinct HLADR+CD38+ CD8 T cells subsets from acute febrile dengue patients

“…IL-18R1 is a receptor for the cytokine IL-18 that mediates IFNγ synthesis (36); IL-18RAP, is an accessory subunit of the IL-18 receptor that leads to the activation of NFkB during cell mediated immunity (37) and CXCR3, a receptor for C-X-C chemokines CXCL9, CXCL10 and CXCL11 that is known to be upregulated on activated effector CD8 T cells and mediates survival and proliferation (38). By contrast, the CD69 - IFNγ - subset showed better expression of cytokine receptors such as CMKLR1, a receptor for chemoattractant chemerin that augments T cell mediated cytotoxicity (39); IL-12RB1, that is a receptor for pro-inflammatory cytokines IL-12 and IL-23 (40); PTGER3, a receptor for prostaglandin E2 that is required for development of fever and has been shown to be critical for IL-17 driven inflammation (41); CSF2RB/IL-15RB1 that is a common beta chain for cytokines IL-3, IL-5 and is regarded as a marker for antigen stimulated cells (42); IL-17RE, that is a receptor for pro-inflammatory cytokine IL-17C (28) and IGF1R, a high affinity receptor for IGF1 and results in the activation of Pi3K-AKT and Ras-MAPK pathways (43) (Figure 3B, Supplementary Table 5) .…”