Page 270 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology ANGPTL8 upregulation in CRC with liver metastasis

1. Introduction of ANGPTL8 in cancer progression and liver metastasis
remains insufficiently explored.
Colorectal cancer (CRC) is the fourth leading cause
of cancer-related mortality, with a low survival rate in Several studies have indicated that ANGPTL8 may act
patients with metastasis. It is estimated that the global as a trigger for cancer cell death. In an in vitro study on
1
CRC incidence will significantly increase by 3.2 million pancreatic cancer, ANGPTL8 was reported to exhibit an
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cases by 2040. CRC is the third most common cancer antiproliferative effect on Mia-PaCa and PANC-1 cell lines.
2
in men and the second most common in women, with Exogenous ANGPTL8 treatment in cancer cell lines has been
a 5-year survival rate. The disease burden of CRC is shown to induce apoptosis. Moreover, ANGPTL8 was found
3
exacerbated by a sedentary lifestyle, lack of physical to reduce cell proliferation in the HepG2 cell line through
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exercise, smoking, and obesity. Recent studies have shown the Wnt signaling pathway. Although previous in vitro
4
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that nutrition can contribute to CRC development, and studies suggest that ANGPTL8 may induce cancer cell
Western diets, coupled with unhealthy lifestyle choices, death, there is a lack of data regarding whether ANGPTL8
are known to accelerate CRC progression. In addition to expression contributes to cancer cell proliferation and
6
these external factors, genetic instability plays a vital role metastasis. Therefore, this study was conducted to establish
in the development of CRC. Notably, recent studies have the baseline data of ANGPTL8 expression in tumors of CRC
7
found that the overall incidence of CRC has increased in patients with and without liver metastasis.
individuals under 50 compared to older individuals. 3,8,9
The increased mortality rate in CRC patients has been 2. Materials and methods
shown to correlate with the metastasis of malignant cells 2.1. Samples
to specific sites within the body. The liver is the most This unicentric, observational clinical study was conducted
common site of CRC metastasis, particularly due to its in Indonesia, involving 41 study participants. Clinical data
association with portal circulation. Approximately were extracted from the hospital database for the period
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25% of CRC patients will develop liver metastasis, between 2021 and 2022. The study was approved by the
which significantly impacts the survival rate of the Institutional Review Board of the Faculty of Medicine,
patients. Liver metastasis in CRC patients presents Universitas Gadjah Mada, Indonesia (ethics approval
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a major clinical problem, with curative resection and number: KE/FK/0938/EC/2021), which granted legal
chemotherapy being the gold standard of treatment. The permission for this clinical study. All participants diagnosed
12
implementation of a preventive management strategy for with CRC who underwent surgery provided written
CRC–liver metastasis would be beneficial for patients, informed consent, in accordance with the Declaration of
potentially involving the development of accurate Helsinki, 1975. This observational clinical study involved
screening procedures, followed by the introduction of 20 CRC patients without liver metastasis and 21 patients
prevention programs aimed at improving the patient’s with liver metastasis. Tumor samples from each group were
quality of life. 13,14 compared to their respective adjacent normal tissues. The
Recent literature has suggested that angiopoietin-like inclusion criteria for this study include: CRC patients with
protein 8 (ANGPTL8) may contribute to dyslipidemia, and without metastasis who had undergone the diagnostic
particularly in relation to triglyceride (TG) metabolism. stage at Dr. Sardjito General Hospital, Yogyakarta; patients
ANGPTL8 is a potential regulator for lipoprotein lipase who had been deemed suitable candidates for surgery;
activity in the vascular system, 15-18 as demonstrated in and those with complete medical records. Patients with
in vitro models. 19-21 Conversely, the inhibition of ANGPTL8 incomplete data, pulmonary metastasis, or those who
upregulation has been shown to reduce TG levels. refused to participate were excluded from this study.
22
ANGPTL8 is also significantly associated with obesity The samples were obtained from Dr. Sardjito General
and related complications. 15,23-31 In addition, significant Hospital in Yogyakarta, Indonesia. Confirmation and
alterations in ANGPTL8 expression have been linked to classification of the samples were determined based on
cancer development and kidney dysfunction, such as histopathological and computed tomography scan data.
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diabetic nephropathy. Previous studies have reported Baseline information of the patients was extracted from
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elevated serum levels of ANGPTL8 in patients with their medical records at the hospital. The primary tumor
hepatocellular carcinoma (HCC) and non-alcoholic fatty samples were stored in the Biobank of the Faculty of
liver disease, 34,35 where ANGPTL8 acts through the Akt- Medicine, Public Health and Nursing, Universitas Gadjah
GSK3β pathway to improve insulin sensitivity. In addition, Mada, and were subsequently transferred to the Molecular
Akt plays a pivotal role in cancer-related survival and Biology Laboratory, Universitas Negeri Malang, for further
proliferation. Despite these findings, the prognostic role analysis.
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Volume 9 Issue 2 (2025) 262 doi: 10.36922/EJMO025080034