Upregulation of APOC1 Promotes Colorectal Cancer Progression and Serves as a Potential Therapeutic Target Based on Bioinformatics Analysis

Weiwei Tang; Hanyuan Liu; Xiao Li; Theng Choon Ooi; Nor Fadilah Rajab; Hongyong Cao; Razinah Sharif

doi:10.1155/2023/2611105

Upregulation of APOC1 Promotes Colorectal Cancer Progression and Serves as a Potential Therapeutic Target Based on Bioinformatics Analysis

J Oncol. 2023 Mar 1:2023:2611105. doi: 10.1155/2023/2611105. eCollection 2023.

Authors

Weiwei Tang^{1

2}, Hanyuan Liu³, Xiao Li³, Theng Choon Ooi¹, Nor Fadilah Rajab¹, Hongyong Cao³, Razinah Sharif^{1

4}

Affiliations

¹ Center for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
² Hepatobiliary, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China.
³ General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Biocompatibility Laboratory, Centre for Research and Instrumentation, University Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia.

Abstract

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.