Page 274 - EJMO-9-2

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

were observed in the current study compared to the trigger cancer cell proliferation, invasion, and migration
previous in vitro investigation. The RNA and protein by mediating antiapoptotic responses. In this study, it
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levels of ANGPTL8 in the tumors of CRC patients with was also found that the expression of ANGPTL8 in the
liver metastasis were found to be higher compared to tumor likely correlates with cell migration. This finding
those without liver metastasis. The higher expression contradicts the previous studies suggesting that ANGPTL8
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of ANGPTL8 inversely correlates with the patient’s body can induce cell apoptosis and proliferation. 39,40 Similar to
weight. Gradual changes in body weight were observed in our findings, previous studies and several databases have
CRC patients following liver metastasis. In line with the reported that ANGPTL8 expression tends to increase in
steady increase of ANGPTL8, the expressions of several colorectal adenocarcinoma, kidney renal clear carcinoma,
genes contributing to tumor metastasis also exhibited an and rectum adenocarcinoma compared to breast cancer,
increase (data not shown). Fundamentally, there are still cholangiocarcinoma, lung adenocarcinoma, and uterine
limited data on how ANGPTL8 is associated with body corpus endometrial carcinoma. 36,54,55 In addition, the
weight loss linked to TG metabolism in CRC patients with expression of ANGPTL8 in the metastasis group is
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liver metastasis. higher than in the non-metastasis group. Moreover, the
predictive property and survival rate analysis of ANGPTL8
In general, loss of ANGPTL8 function or even expression suggest that this liver hormone could
downregulation of ANGPTL8 expression could improve significantly and potentially serve as a biomarker in those
TG metabolism and reduce the progression of obesity cancers. However, it remains unclear whether the higher
and hypertriglyceridemia. 50,51 A previous in vivo study expression of this hormone at the tumor site will trigger
demonstrated that ANGPTL8 influences adipose formation, an increase in glucose synthesis to support malignant cell
and the knockout of ANGPTL8 resulted in significantly growth and facilitate detachment from the original site to
reduced TG levels in adipose tissue compared to wild-type the liver.
mice, suggesting that ANGPTL8 may be involved in the
regulation of TG. Moreover, the potential mechanism by Collectively, the preliminary findings of this study
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which ANGPTL8 increases TG levels involves facilitating propose a hypothetical framework suggesting that
the cleavage of ANGPTL3, thereby releasing its N-terminal ANGPTL8 could be a potential contributor and part of a
domain, which suppresses lipoprotein lipase activity and panel of markers for CRC with liver metastasis. However,
promotes adipose tissue decomposition. The variation in there are several limitations in this study. For instance, our
ANGPTL8 response or expression in the tumor may be clinical investigation could not provide a comprehensive
influenced by body weight loss progression. A previous database for the baseline data of the patients. In addition,
our study focused solely on the fundamental profile
study suggested that impaired ANGPTL8 response can analysis of ANGPTL8 expression in the tumors of CRC
be restored after weight loss. However, in this study, it patients, without any supporting data from serological
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remains unclear whether the gradual weight loss observed markers or other metabolic factors related to ANGPTL8.
in CRC patients with liver metastasis contributes to the Future investigations are warranted, involving a larger
elevated ANGPTL8 expression in the tumor. Another sample size, comparisons across different racial groups
possible mechanism is that reduced ANGPTL8 expression of clinical patients, and further laboratory analyses.
in the liver, possibly due to liver dysfunction-linked liver A comprehensive correlational approach that includes
metastasis, could lead to hyperglycemia and impaired microscopic, serological, and bioinformatics analysis will
insulin sensitivity. This could consequently drive increased be essential to support these preliminary findings.
fat metabolism in adipose tissue, leading to body weight
loss. 5. Conclusion
Based on the previous study, it was suggested that The findings of this study suggest that ANGPTL8 may
ANGPTL8 could improve insulin sensitivity through the contribute to the development of tumor-associated
Akt-GSK3β pathway and contribute to cancer cell survival metastasis in CRC patients. The observed changes in
and proliferation through the Akt signaling pathway. ANGPTL8 expression are hypothesized to correlate with
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In line with this finding, our data show that glucose body weight loss in CRC patients with liver metastasis.
levels in CRC patients with liver metastasis are higher This study highlights the potential of ANGPTL8 not only
compared to those without metastasis. It is predicted that as a therapeutic target but also as a promising prognostic
the steadily increasing glucose levels may promote cell marker for CRC. Future investigations, including larger
proliferation, survival, and metastasis in the local tumor sample sizes and comprehensive analyses, are warranted
sites. In addition, disturbances in glucose levels – caused to validate these findings and fully explore the clinical
by abnormal glucose metabolism – could potentially application of ANGPTL8 in managing CRC.

Volume 9 Issue 2 (2025) 266 doi: 10.36922/EJMO025080034