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载脂蛋白C1(APOC1)表达降低抑制了癌症进展,并与食管癌的更好预后和免疫微环境相关。

Decreased APOC1 expression inhibited cancer progression and was associated with better prognosis and immune microenvironment in esophageal cancer.

作者信息

Guo Qiang, Liu Xiao-Li, Jiang Ni, Zhang Wen-Jun, Guo Shao-Wen, Yang Heng, Ji Yan-Mei, Zhou Jun, Guo Jia-Long, Zhang Jun, Liu Hua-Song

机构信息

Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine Shiyan, Hubei, China.

Department of Ultrasound, The People's Hospital of Jianyang City Jianyang, Sichuan, China.

出版信息

Am J Cancer Res. 2022 Nov 15;12(11):4904-4929. eCollection 2022.

Abstract

Several studies have demonstrated the involvement of apolipoprotein C1 (APOC1) in multiple cancers. However, the role of APOC1 in esophageal cancer (ESCA) has not been elucidated. Hence, we examined the expression of APOC1 in ESCA tissues acquired from The Cancer Genome Atlas (TCGA) database and clinical samples from our hospital. An investigation of the association of APOC1 with the clinicopathological characteristics, prognosis, and diagnosis of ESCA was carried out on the basis of survival, receiver operating characteristics, and correlation analyses. Gene ontology, KEGG analysis, and protein-protein interaction network showed that co-expressed APOC1 genes were involved in the functions, mechanisms, and action network. The effects of APOC1 expression on ESCA cells were explored using CCK-8, migration and invasion assays. The relationship between APOC1 expression and ESCA immune-infiltrating cells and cell markers were examined using correlation analysis. We found that APOC1 was overexpressed in TCGA ESCA tissues and the same was validated in clinical ESCA tissues, with the area under the curve for APOC1 being 0.887. Overexpression of APOC1 was associated with short overall survival, disease-specific survival, progression-free interval, T stage, pathological stage, body mass index, and histological grade. Inhibition of APOC1 expression significantly reduced the proliferation, migration, and invasion of ESCA cells. Furthermore, APOC1 expression positively correlated with the ESTIMATE, immune, and stromal scores in ESCA. Overexpression of APOC1 correlated with the tumor purity, B cells, T helper cells, natural killer cells, cytotoxic cells, and other immune cells. Moreover, APOC1 was involved in ESCA progression via T cell receptor, B cell receptor, and other immune signaling pathways. Thus, APOC1 overexpression is expected to be a biomarker for dismal prognosis and diagnosis of ESCA. Inhibition of APOC1 expression significantly reduced the proliferation, migration, and invasion of ESCA cells. Overexpression of APOC1 was associated with the immune microenvironment in ESCA. Thus, APOC1 may be an efficient biomarker for proper prognosis and diagnosis of ESCA.

摘要

多项研究已证明载脂蛋白C1(APOC1)与多种癌症有关。然而,APOC1在食管癌(ESCA)中的作用尚未阐明。因此,我们检测了从癌症基因组图谱(TCGA)数据库获取的ESCA组织以及我院临床样本中APOC1的表达情况。基于生存分析、受试者工作特征分析和相关性分析,对APOC1与ESCA的临床病理特征、预后及诊断的相关性进行了研究。基因本体论、KEGG分析和蛋白质-蛋白质相互作用网络显示,共表达的APOC1基因参与了相关功能、机制及作用网络。使用CCK-8、迁移和侵袭试验探究了APOC1表达对ESCA细胞的影响。通过相关性分析检测了APOC1表达与ESCA免疫浸润细胞及细胞标志物之间的关系。我们发现APOC1在TCGA ESCA组织中过表达,临床ESCA组织中也得到验证,APOC1的曲线下面积为0.887。APOC1过表达与总生存期短、疾病特异性生存期短、无进展生存期短、T分期、病理分期、体重指数和组织学分级相关。抑制APOC1表达显著降低了ESCA细胞的增殖、迁移和侵袭能力。此外,APOC1表达与ESCA中的ESTIMATE评分、免疫评分和基质评分呈正相关。APOC1过表达与肿瘤纯度、B细胞、辅助性T细胞、自然杀伤细胞、细胞毒性细胞及其他免疫细胞相关。此外,APOC1通过T细胞受体、B细胞受体及其他免疫信号通路参与ESCA进展。因此,APOC1过表达有望成为ESCA预后不良及诊断的生物标志物。抑制APOC1表达显著降低了ESCA细胞的增殖、迁移和侵袭能力。APOC1过表达与ESCA的免疫微环境相关。因此,APOC1可能是ESCA正确预后及诊断的有效生物标志物。

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