Zhu Ningning, Yang Yueyang, Wang Haitong, Tang Peng, Zhang Hongdian, Sun Haiyan, Gong Lei, Yu Zhentao
Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital; National, Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and PeKing Union Medical College, Shenzhen, China.
Front Oncol. 2022 Apr 28;12:822849. doi: 10.3389/fonc.2022.822849. eCollection 2022.
The 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).
The 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.
We 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.
CSF2RB 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.
肿瘤微环境在肿瘤的发生和发展中起重要作用。然而，在理解肿瘤细胞与免疫肿瘤微环境（TME）之间的分子和细胞相互作用方面仍存在差距。本研究的目的是鉴定一个在肺腺癌（LUAD）肿瘤微环境中起重要作用的新基因。
从TCGA数据库下载LUAD的基因表达谱和临床数据。首先，我们使用ESTIMATE算法相应地评估免疫和基质评分。此外，我们分析了高、低免疫/基质评分组中差异表达的免疫相关基因（IRG）。然后，我们使用蛋白质-蛋白质相互作用网络（PPI网络）和单变量Cox回归分析来鉴定枢纽基因。之后，我们分析了CSF2RB表达与TNM分期/预后之间的关系。此外，基因集富集分析（GSEA）用于分析CSF2RB调控的通路，Pearson相关分析方法用于分析CSF2RB与免疫细胞之间的相关性。最后，我们使用蛋白质免疫印迹法、实时定量PCR（RT-qPCR）和免疫组织化学（IHC）来验证CSF2RB在癌组织和癌旁组织中的表达。
我们发现CSF2RB在LUAD肿瘤微环境中起重要作用。CSF2RB在肿瘤组织中的表达低于正常组织。此外，Kaplan-Meier生存曲线分析表明CSF2RB低表达与较差的生存率相关，多变量COX回归分析显示CSF2RB基因是预后的独立危险因素，与患者是否接受化疗或放疗无关。更重要的是，CSF2RB高表达与早期T、N和临床分期相关。GSEA分析显示CSF2RB与多种免疫相关通路有关，包括T细胞受体信号通路、Toll样受体信号通路和B细胞受体信号通路。CSF2RB表达水平也与LUAD中浸润性CD4+T细胞、巨噬细胞、NK细胞和单核细胞的水平呈正相关。最后，使用LUAD患者的肿瘤组织评估CSF2RB表达。肿瘤部位的表达明显低于相邻正常组织，这与数据分析结果一致。
CSF2RB可有效预测肺腺癌患者的预后，也可能是癌症治疗和预防的潜在靶点。然而，需要进一步研究阐明CSF2RB的功能和调控机制，并开发一些新的治疗策略。
