Thailand medical researchers identify new biomarkers ACSL4, SLC7A11, and CHAC1 for improved Cholangiocarcinoma prognosis

Thailand Medical: Cholangiocarcinoma (CCA) is a rare but aggressive cancer that develops in the bile ducts, primarily affecting the liver and biliary tract. This type of cancer is particularly common in Southeast Asia, especially northeastern Thailand. Despite advances in medical research, diagnosing and treating CCA remains challenging, often because patients are diagnosed in later stages. However, a recent study from Khon Kaen University in Thailand, sheds light on promising new biomarkers that could help improve the prognosis of Cholangiocarcinoma patients. This Thailand Medical News report will explore how proteins ACSL4, SLC7A11, and CHAC1 play a crucial role in CCA and how their presence could guide better treatment options.


Thailand medical researchers identify new biomarkers ACSL4, SLC7A11, and
CHAC1 for improved Cholangiocarcinoma prognosis

Cholangiocarcinoma: A Silent Threat
Cholangiocarcinoma is a cancer that originates from the epithelial cells of the bile ducts. Though it is uncommon in the West, CCA is a major health concern in Thailand, primarily due to chronic liver fluke infections. Often called a "silent killer," CCA rarely shows symptoms in its early stages, leading to late diagnoses when the disease has progressed. This leads to poor survival rates, with only 8.1% of patients living two years post-diagnosis. Surgery is the primary treatment, but only 20.6% of those who undergo surgery survive more than five years.
 
Given the grim prognosis for patients, identifying reliable biomarkers that can predict the course of the disease is critical. Biomarkers such as carbohydrate antigen 19-9 (CA19-9) have been studied, but their sensitivity and specificity remain limited. This article highlights new research on ferroptosis-related proteins ACSL4, SLC7A11, and CHAC1, which offer hope for improving diagnosis and prognosis in CCA patients.
 
Ferroptosis and Its Role in Cancer
Ferroptosis is a type of regulated cell death caused by an accumulation of iron and lipid peroxides in the body. While ferroptosis can be a defense mechanism against rapidly growing cancer cells, cancer cells can develop resistance by producing antioxidants to survive. Researchers have found that proteins involved in this process, like ACSL4, SLC7A11, and CHAC1, play crucial roles in regulating cell death and may serve as biomarkers or therapeutic targets in several types of cancer.
 
The Study Findings
The study team investigated the expression of ACSL4, SLC7A11, and CHAC1 in cholangiocarcinoma tissue samples from 137 patients, as well as serum samples from 61 patients. The institutions involved in this study included the Centre for Research and Development of Medical Diagnostic Laboratories (CMDL) and the Cholangiocarcinoma Research Institute, both part of Khon Kaen University.
 
ACSL4, SLC7A11, and CHAC1 are proteins linked to ferroptosis, and their levels were measured through immunohistochemistry in tissue samples and ELISA in serum samples. The study found that ele vated levels of these proteins were associated with poorer prognosis in CCA patients, offering a potential biomarker panel for better diagnosis and prognosis.
 
Key Findings on ACSL4
ACSL4 plays a key role in lipid metabolism, which can influence ferroptosis. In this study, ACSL4 was found in higher concentrations in patients with more aggressive types of cholangiocarcinoma, such as the extrahepatic type. High levels of ACSL4 were also linked to abnormal liver function, indicated by elevated alanine transferase (ALT) levels, and advanced tumor stages.
 
The researchers noted that ACSL4 might serve as an early marker for identifying aggressive CCA cases. This means that measuring ACSL4 levels could help physicians predict which patients are likely to face rapid disease progression, allowing for earlier interventions.
 
SLC7A11: A Marker for Advanced CCA
SLC7A11 is another important protein involved in preventing cell death by managing the balance of certain amino acids. Elevated SLC7A11 levels were found in patients with more advanced tumors, making it another valuable marker for identifying the severity of CCA. Patients with high levels of SLC7A11 also exhibited poor survival rates compared to those with lower levels. Interestingly, SLC7A11 may also serve as a therapeutic target, as inhibiting its function could induce ferroptosis in cancer cells, leading to their destruction.
 
CHAC1 and Patient Survival
CHAC1, which degrades glutathione, is another key player in ferroptosis. The study found that high CHAC1 levels were significantly linked to shorter survival times in patients with cholangiocarcinoma. Patients with elevated CHAC1 levels had a median survival time of just 9.2 months, compared to 12.8 months for those with lower levels of the protein.
 
The researchers noted that CHAC1 could be an important target for future therapies aimed at prolonging survival in CCA patients. This finding is particularly relevant for patients who have survived two years post-diagnosis, as high CHAC1 levels continued to indicate a poorer prognosis.
 
Serum Biomarkers: A Less Invasive Diagnostic Tool
One of the most promising aspects of this study is the discovery that ACSL4 and SLC7A11 can be detected in the serum of CCA patients. This means that patients could potentially be monitored using a simple blood test, which would be far less invasive than tissue biopsies. In the study, patients with advanced CCA had significantly higher serum levels of ACSL4 and SLC7A11 compared to those with early-stage CCA.
 
Elevated serum ACSL4 levels were associated with worse overall survival, with patients in the high ACSL4 group living a median of 6.2 months, compared to nearly 43 months in the low ACSL4 group. Similarly, high SLC7A11 levels were linked to shorter survival times, suggesting that these proteins could be useful for monitoring disease progression in CCA patients.
 
Conclusion
This research highlights the importance of ACSL4, SLC7A11, and CHAC1 as potential biomarkers for cholangiocarcinoma. These proteins not only help predict the aggressiveness of the disease but may also offer targets for future therapies that could induce ferroptosis and eliminate cancer cells. By detecting these proteins in serum, physicians could have access to less invasive diagnostic tools, improving patient outcomes by allowing for earlier intervention.
 
The study also underscores the need for further research into the role of these proteins in CCA and how they can be used in clinical practice. Expanding the sample size and investigating the potential of targeting ACSL4, SLC7A11, and CHAC1 in treatment could lead to significant advancements in the fight against cholangiocarcinoma.
 
The study findings were published in the peer-reviewed journal: Biomedicines.
https://www.mdpi.com/2227-9059/12/9/2091
 
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