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Updated: Oct 5, 2025
An Efficient Method for Directed Hepatocyte-Like Cell Induction from Human Embryonic Stem Cells
Published on: May 6, 2021
New stem cell autophagy surrogate diagnostic biomarkers in early-stage hepatocellular carcinoma in Egypt: A pilot
Tarek Yosef1, Wesam Ahmed Ibrahim1, Marwa Matboli2
1Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt.
Background:
Stem cell autophagy disruption is responsible for the development of hepatocellular carcinoma (HCC). Many non-coding RNAs are linked to the activation and inhibition of certain genes. The SQSTM1 gene controls stem cell autophagy as shown in previous studies. The upregulation of SQSTM1 is associated with the inhibition of autophagy in cancerous stem cells in patients with HCC.
Aim:
To determine whether serum microRNA, hsa-miR-519d, is linked to SQSTM1 gene and whether they could be used as diagnostic biomarkers for early-stage HCC.
Methods:
In silico analysis was performed to determine the most correlated genes of autophagy with microRNAs. SQSTM1 and hsa-miR-519d were validated through this pilot clinical study. This study included 50 Egyptian participants, who were classified into three subgroups: Group 1 included 34 patients with early-stage HCC, Group 2 included 11 patients with chronic liver disease, and Group 3 (control) included 5 healthy subjects. All patients were subjected to full laboratory investigations, including viral markers and alpha-fetoprotein (AFP), abdominal ultrasound, and clinical assessment with the Child-Pugh score calculation. Besides, the patients with HCC underwent triphasic computed tomography with contrast to diagnose and determine the tumor site, size, and number. Quantitative real-time polymerase chain reaction was used to assess hsa-miR-519d-3p and SQSTM1 in the serum of all the study participants.
Results:
Hsa-miR-519d-3p was significantly upregulated in patients with HCC compared with those with chronic liver disease and healthy subjects with an area under the curve (AUC) of 0.939, with cutoff value 8.34, sensitivity of 91.2%, and specificity of 81.8%. SQSTM1 was upregulated with an AUC of 0.995, with cutoff value 7.89, sensitivity of 97.1%, and specificity of 100%. AFP significantly increased in patients with HCC with an AUC of 0.794, with cutoff value 7.30 ng/mL, sensitivity of 76.5%, and specificity of 72.7%.
Conclusion:
This study is the first to show a direct relation between SQSTM1 and hsa-miR-519d-3p; they are both upregulated in HCC. Thus, they could be used as surrogate diagnostic markers for stem cell autophagy disturbance in early-stage HCC.
Insights
This study found that hsa-miR-519d and SQSTM1 are upregulated in hepatocellular carcinoma (HCC) and can serve as biomarkers for early-stage disease. These findings highlight their potential for diagnosing stem cell autophagy disruption in HCC patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Autophagy disruption in stem cells is implicated in hepatocellular carcinoma (HCC) development.
- The SQSTM1 gene regulates stem cell autophagy, and its upregulation inhibits autophagy in HCC stem cells.
Purpose of the Study:
- To investigate the relationship between serum microRNA, hsa-miR-519d, and the SQSTM1 gene.
- To evaluate their potential as diagnostic biomarkers for early-stage HCC.
Main Methods:
- In silico analysis to identify microRNA-gene correlations in autophagy.
- Clinical validation in 50 Egyptian participants (early HCC, chronic liver disease, healthy controls).
- Quantitative real-time PCR to measure serum hsa-miR-519d-3p and SQSTM1 levels.
Main Results:
- Hsa-miR-519d-3p was significantly upregulated in HCC patients (AUC=0.939).
- SQSTM1 was also upregulated in HCC patients (AUC=0.995), showing high sensitivity and specificity.
- Alpha-fetoprotein (AFP) was elevated in HCC patients (AUC=0.794).
Conclusions:
- This study establishes a direct link between SQSTM1 and hsa-miR-519d, both upregulated in HCC.
- These molecules show promise as surrogate diagnostic markers for stem cell autophagy disturbance in early-stage HCC.
