Related Experiment Video
Updated: Jul 25, 2025
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Alteration of STK11 Expression Associated With Cholangiocarcinoma Progression
Papitchaya Sirithawat1,2, Apinya Jusakul2,3, Sarinya Kongpetch2,4
1Medical Science Program, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Background/Aim:
Serine/threonine kinase 11 (STK11), a tumor suppressor, controls 5' AMP-activated protein kinase (AMPK) signaling in a variety of cellular functions. Mutated STK11 has been identified as a novel driver gene that promotes cancer progression. The purpose of this study was to investigate the alteration of STK11 and its correlation with clinicopathological data in cholangiocarcinoma (CCA).
Materials And Methods:
Gene mutation and expression analyses were performed using cBioportal and Gene Expression Profiling Interactive Analysis version 2 (GEPIA2). qRT-PCR was performed to measure STK11 mRNA levels and immunohistochemistry was performed to investigate STK11 protein expression in CCA tissues.
Results:
The results from publicly available cancer datasets showed that 2.7% of CCA cases had STK11 mutations. Most of STK11 gene mutations are of the truncating type and result in low STK11 mRNA and protein expression. We detected a correlation between STK11 mutation status and the tendency for shorter patient survival. The results of qRT-PCR revealed that STK11 mRNA levels were statistically significantly lower in CCA patients with mutated STK11 compared to those with wild-type STK11 (p-value=0.013). Immunohistochemical staining showed high STK11 expression in 43.8% and low expression in 56.2% of CCA tissues examined. Low STK11 protein expression resulted in poor prognosis compared with high STK11 expression, especially in CCA papillary carcinoma. Univariate and multivariate analysis revealed that high STK11 expression was associated with a decreased hazard ratio of patient survival rates (HR=0.696, p-value=0.06 and HR=0.666, p-value=0.04, respectively).
Conclusion:
Alteration of STK11 mutational or mRNA/protein status might be used as a potential predictive biomarker for the prognosis of the clinical outcomes in CCA patients.
Insights
Alterations in the STK11 gene, a tumor suppressor, are linked to poorer outcomes in cholangiocarcinoma (CCA). Low STK11 expression correlates with reduced survival, suggesting its potential as a predictive biomarker for CCA prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Serine/threonine kinase 11 (STK11) is a critical tumor suppressor regulating AMPK signaling.
- Mutations in STK11 are increasingly recognized as drivers of cancer progression.
- Cholangiocarcinoma (CCA) is a challenging malignancy with a need for better prognostic markers.
Purpose of the Study:
- To investigate STK11 alterations (mutations, mRNA, and protein expression) in cholangiocarcinoma.
- To correlate STK11 status with clinicopathological features and patient survival.
- To evaluate STK11 as a potential predictive biomarker for CCA outcomes.
Main Methods:
- Analysis of STK11 mutations and expression using cBioportal and GEPIA2.
- Quantitative real-time PCR (qRT-PCR) for STK11 mRNA levels.
- Immunohistochemistry for STK11 protein expression in CCA tissues.
Main Results:
- STK11 mutations were found in 2.7% of CCA cases, often leading to truncating mutations and reduced expression.
- Lower STK11 mRNA and protein levels were significantly associated with shorter patient survival, particularly in papillary CCA.
- High STK11 expression correlated with a decreased hazard ratio for patient survival.
Conclusions:
- STK11 gene alterations, including mutations and altered expression, are relevant in CCA.
- STK11 status may serve as a valuable predictive biomarker for clinical outcomes in cholangiocarcinoma patients.
- Further research into STK11's role could inform targeted therapeutic strategies for CCA.
