全面分析 FABP4 在结肠腺癌中的免疫意义。
Comprehensive analysis of the immune implication of FABP4 in colon adenocarcinoma.
机构信息
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
出版信息
PLoS One. 2022 Oct 20;17(10):e0276430. doi: 10.1371/journal.pone.0276430. eCollection 2022.
BACKGROUND
Fatty acid-binding protein 4 (FABP4) has been reported to be associated with tumor progress and poor prognosis in various cancers. However, the relationship between FABP4 expression and tumor immunity in colon adenocarcinoma (COAD) is still poorly understood.
METHODS
FABP4 mRNA expression was analyzed using The Cancer Genome Atlas (TCGA)-COAD data. FABP4 protein staining was performed by immunohistochemistry (IHC) staining in our 10 paired COAD samples and corresponding adjacent noncancerous tissues. The association between FABP4 and immune cell infiltration was evaluated by Tumor Immune Estimation Resource (TIMER) database. FABP4 coexpressed genes were identified based on Cancer Cell Line Encyclopedia (CCLE) database, which were employed for further enrichment analysis. FABP4 related immunomodulators was identified by Tumor and Immune System Interaction Database (TISIDB) database, and a prognostic risk signature was constructed based on FABP4-related immunomodulators using stepwise Cox regression analysis. A nomogram consists of FABP4 related immunomodulators signature and clinical parameters was developed to predict the overall survival (OS).
RESULTS
In TCGA data, we found that the decreased FABP4 mRNA expression in COAD samples compared with normal samples, and low FABP4 mRNA expression was associated with B cells, CD4+ T cells, CD8+ T cells, myeloid dendritic cells, macrophages, and neutrophils. In our 10 paired samples, the protein levels of COAD were lower in all COAD tissues than in their adjacent noncancerous tissues. Functional enrichment analysis revealed that FABP4 coexpressed genes were mostly enriched in immune-related pathways. Based on 54 FABP4-related immunomodulators, a 2-gene FABP4-related prognostic risk signature was developed, and the signature stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The Nomogram consists of the prognostic signature and clinical parameters had a certain predictability for prognosis of COAD patients.
CONCLUSION
These findings suggest that FABP4 is associated with 2-gene immune signature which also correlate with the prognosis of COAD patients.
背景
脂肪酸结合蛋白 4（FABP4）已被报道与多种癌症的肿瘤进展和不良预后相关。然而，FABP4 表达与结肠腺癌（COAD）肿瘤免疫之间的关系仍知之甚少。
方法
使用癌症基因组图谱（TCGA）-COAD 数据对 FABP4 mRNA 表达进行分析。通过免疫组织化学（IHC）染色对我们的 10 对 COAD 样本及其相应的相邻非癌组织进行 FABP4 蛋白染色。通过肿瘤免疫估计资源（TIMER）数据库评估 FABP4 与免疫细胞浸润的相关性。根据癌症细胞系百科全书（CCLE）数据库确定 FABP4 共表达基因，并进行进一步的富集分析。通过肿瘤和免疫系统相互作用数据库（TISIDB）数据库确定 FABP4 相关免疫调节剂，并基于 FABP4 相关免疫调节剂使用逐步 Cox 回归分析构建预后风险特征。根据 FABP4 相关免疫调节剂和临床参数构建列线图以预测总生存期（OS）。
结果
在 TCGA 数据中，我们发现 COAD 样本中 FABP4 mRNA 表达降低，与正常样本相比，低 FABP4 mRNA 表达与 B 细胞、CD4+T 细胞、CD8+T 细胞、髓样树突状细胞、巨噬细胞和中性粒细胞相关。在我们的 10 对样本中，COAD 组织中的蛋白水平均低于其相邻非癌组织。功能富集分析显示，FABP4 共表达基因主要富集在免疫相关通路中。基于 54 个 FABP4 相关免疫调节剂，建立了一个 2 基因 FABP4 相关预后风险特征，该特征将患者分为高风险和低风险组，具有统计学上不同的生存结果。由预后特征和临床参数组成的列线图对 COAD 患者的预后有一定的预测能力。
结论
这些发现表明，FABP4 与与 COAD 患者预后相关的 2 基因免疫特征相关。
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