Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Pathol Oncol Res. 2023 Mar 8;29:1610976. doi: 10.3389/pore.2023.1610976. eCollection 2023.
Esophageal carcinoma (ESCA), a common malignant tumor of the digestive tract with insidious onset, is a serious threat to human health. Despite multiple treatment modalities for patients with ESCA, the overall prognosis remains poor. Apolipoprotein C1 (APOC1) is involved in tumorigenesis as an inflammation-related molecule, and its role in esophageal cancer is still unknown. We downloaded documents and clinical data using The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. We also conducted bioinformatics studies on the diagnostic value, prognostic value, and correlation between APOC1 and immune infiltrating cells in ESCA through STRING (https://cn.string-db.org/), the TISIDB (http://cis.hku.hk/TISIDB/) website, and various other analysis tools. In patients with ESCA, APOC1 was significantly more highly expressed in tumor tissues than in normal tissues ( < 0.001). APOC1 could diagnose ESCA more accurately and determine the TNM stage and disease classification with high accuracy (area under the curve, AUC≥0.807). The results of the Kaplan-Meier curve analysis showed that APOC1 has prognostic value for esophageal squamous carcinoma (ESCC) ( = 0.043). Univariate analysis showed that high APOC1 expression in ESCC was significantly associated with worse overall survival (OS) ( = 0.043), and multivariate analysis shows that high APOC1 expression was an independent risk factor for the OS of patients with ESCC ( = 0.030). In addition, the GO (gene ontology)/KEGG (Kyoto encyclopedia of genes and genomes) analysis showed a concentration of gene enrichment in the regulation of T-cell activation, cornification, cytolysis, external side of the plasma membrane, MHC protein complex, MHC class II protein complex, serine-type peptidase activity, serine-type endopeptidase activity, infection, antigen processing and presentation, and graft-versus-host disease (all < 0.001). GSEA (gene set enrichment analysis) showed that enrichment pathways such as immunoregulatory-interactions between a lymphoid and non-lymphoid cell (NES = 1.493, p. adj = 0.023, FDR = 0.017) and FCERI-mediated NF-KB activation (NES = 1.437, p. adj = 0.023, FDR = 0.017) were significantly enriched in APOC1-related phenotypes. In addition, APOC1 was significantly associated with tumor immune infiltrating cells and immune chemokines. APOC1 can be used as a prognostic biomarker for esophageal cancer. Furthermore, as a novel prognostic marker for patients with ESCC, it may have potential value for further investigation regarding the diagnosis and treatment of this group of patients.
食管癌(ESCA)是一种起病隐匿的消化道常见恶性肿瘤,严重威胁人类健康。尽管 ESCA 患者有多种治疗方法,但总体预后仍较差。载脂蛋白 C1(APOC1)作为一种与炎症相关的分子参与肿瘤发生,但其在食管癌中的作用尚不清楚。
我们使用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载了文献和临床数据。我们还通过 STRING(https://cn.string-db.org/)、TISIDB(http://cis.hku.hk/TISIDB/)网站和其他各种分析工具,对 ESCA 中 APOC1 的诊断价值、预后价值以及与免疫浸润细胞的相关性进行了生物信息学研究。
在 ESCA 患者中,肿瘤组织中 APOC1 的表达明显高于正常组织(<0.001)。APOC1 可以更准确地诊断 ESCA,并具有高准确性地确定 TNM 分期和疾病分类(曲线下面积,AUC≥0.807)。Kaplan-Meier 曲线分析结果表明,APOC1 对食管鳞状细胞癌(ESCC)具有预后价值(=0.043)。单因素分析显示,ESCC 中 APOC1 高表达与总生存期(OS)较差显著相关(=0.043),多因素分析表明,APOC1 高表达是 ESCC 患者 OS 的独立危险因素(=0.030)。此外,GO(基因本体论)/KEGG(京都基因与基因组百科全书)分析显示,基因富集集中在 T 细胞激活、角质化、细胞溶解、质膜外、MHC 蛋白复合物、MHC Ⅱ类蛋白复合物、丝氨酸型肽酶活性、丝氨酸型内肽酶活性、感染、抗原加工和呈递以及移植物抗宿主病等方面(均<0.001)。GSEA(基因集富集分析)显示,APOC1 相关表型中富含免疫调节性-淋巴样细胞和非淋巴样细胞之间的相互作用(NES=1.493,p.adj=0.023,FDR=0.017)和 FCERI 介导的 NF-KB 激活(NES=1.437,p.adj=0.023,FDR=0.017)等途径明显富集。此外,APOC1 与肿瘤免疫浸润细胞和免疫趋化因子显著相关。
APOC1 可作为食管癌的预后生物标志物。此外,作为 ESCC 患者的一种新的预后标志物,它可能对进一步研究该组患者的诊断和治疗具有潜在价值。