Background. Approximately 10% of cancer patients worldwide have colorectal cancer (CRC), a prevalent gastrointestinal malignancy with substantial mortality and morbidity. The purpose of this work was to investigate the APOC1 gene’s expression patterns in the CRC tumor microenvironment and, using the findings from bioinformatics, to assess the biological function of APOC1 in the development of CRC. Methods. The TCGA portal was employed in this investigation to find APOC1 expression in CRC. Its correlation with other genes and clinicopathological data was examined using the UALCAN database. To validate APOC1’s cellular location, the Human Protein was employed. In order to forecast the relationship between APOC1 expression and prognosis in CRC patients, the Kaplan–Meier plotter database was used. TISIDB was also employed to evaluate the connection between immune responses and APOC1 expression in CRC. The interactions of APOC1 with other proteins were predicted using STRING. In order to understand the factors that contribute to liver metastasis from CRC, single-cell RNA sequencing (scRNA-seq) was done on one patient who had the disease. This procedure included sampling preoperative blood and the main colorectal cancer tissues, surrounding colorectal cancer normal tissues, liver metastatic cancer tissues, and normal liver tissues. Finally, an in vitro knockdown method was used to assess how APOC1 expression in tumor-associated macrophages (TAMs) affected CRC cancer cell growth and migration. Results. When compared to paracancerous tissues, APOC1 expression was considerably higher in CRC tissues. The clinicopathological stage and the prognosis of CRC patients had a positive correlation with APOC1 upregulation and a negative correlation, respectively. APOC1 proteins are mostly found in cell cytosols where they may interact with APOE, RAB42, and TREM2. APOC1 was also discovered to have a substantial relationship with immunoinhibitors (CD274, IDO1, and IL10) and immunostimulators (PVR, CD86, and ICOS). According to the results of scRNA-seq, we found that TAMs of CRC tissues had considerably more APOC1 than other cell groups. The proliferation and migration of CRC cells were impeded in vitro by APOC1 knockdown in TAMs. Conclusion. Based on scRNA-seq research, the current study shows that APOC1 was overexpressed in TAMs from CRC tissues. By inhibiting APOC1 in TAMs, CRC progression was reduced in vitro, offering a new tactic and giving CRC patients fresh hope.

中文翻译：

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APOC1上调促进结直肠癌进展并作为基于生物信息学分析的潜在治疗靶点

背景。全世界大约 10% 的癌症患者患有结直肠癌 (CRC)，这是一种常见的胃肠道恶性肿瘤，死亡率和发病率都很高。这项工作的目的是研究 APOC1 基因在 CRC 肿瘤微环境中的表达模式，并利用生物信息学的发现来评估 APOC1 在 CRC 发展中的生物学功能。方法. 本次调查采用 TCGA 门户网站来查找 CRC 中的 APOC1 表达。使用 UALCAN 数据库检查其与其他基因和临床病理学数据的相关性。为了验证 APOC1 的细胞定位，使用了人类蛋白。为了预测 APOC1 表达与 CRC 患者预后之间的关系，使用了 Kaplan-Meier 绘图仪数据库。TISIDB 还用于评估 CRC 中免疫反应与 APOC1 表达之间的联系。使用 STRING 预测 APOC1 与其他蛋白质的相互作用。为了了解导致 CRC 肝转移的因素，对一名患有该病的患者进行了单细胞 RNA 测序 (scRNA-seq)。该程序包括采集术前血液和主要结直肠癌组织，周围结直肠癌正常组织、肝转移癌组织、正常肝组织。最后，使用体外敲低方法评估肿瘤相关巨噬细胞 (TAM) 中的 APOC1 表达如何影响 CRC 癌细胞的生长和迁移。结果。与癌旁组织相比，APOC1 表达在 CRC 组织中明显更高。CRC患者的临床病理分期和预后分别与APOC1上调呈正相关和负相关。APOC1 蛋白主要存在于细胞胞质溶胶中，它们可能与 APOE、RAB42 和 TREM2 相互作用。还发现 APOC1 与免疫抑制剂（CD274、IDO1 和 IL10）和免疫刺激剂（PVR、CD86 和 ICOS）有实质性关系。根据 scRNA-seq 的结果，我们发现 CRC 组织的 TAMs 比其他细胞群具有更多的 APOC1。TAM 中的 APOC1 敲低在体外阻碍了 CRC 细胞的增殖和迁移。结论. 基于 scRNA-seq 研究，目前的研究表明 APOC1 在来自 CRC 组织的 TAM 中过表达。通过抑制 TAM 中的 APOC1，可在体外减少 CRC 进展，提供新策略并为 CRC 患者带来新希望。