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SQSTM1 Expression in Hepatocellular Carcinoma and Relation to Tumor Recurrence After Radiofrequency Ablation
Amr Abdel-Moety1, Nahed Baddour2, Perihan Salem1
1Department of Internal Medicine (Hepatobiliary Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Background/Aims:
Autophagy is a process that allows the degradation of detrimental components through the lysosome to maintain cellular homeostasis under variable stimuli. SQSTM1 is a key molecule involved in functional autophagy and is linked to different signaling pathways, oxidative responses, and inflammation. Dysregulation of autophagy is reported in a broad spectrum of diseases. Accumulation of SQSTM1 reflects impaired autophagy, which is related to carcinogenesis and progression of various tumors, including hepatocellular carcinoma (HCC). This study investigated SQSTM1 protein expression in HCC and its relation to the clinicopathological features and the likelihood of tumor recurrence after radiofrequency ablation (RFA).
Methods:
This study included 50 patients with cirrhotic HCC of Barcelona Clinic Liver Cancer stages 0/A-B eligible for RFA. Tumor and peritumor biopsies were obtained just prior to local ablation and assessed for tumor pathological grade and SQSTM1 expression by immunohistochemistry. Patients were followed for one year after achieving complete ablation to detect any tumor recurrence.
Results:
Serum alpha-fetoprotein level (U = 149.50, P = 0.027∗) and pathological grade of the tumor (χ2 = 12.702, P = 0.002∗) associated significantly with the tumor response to RFA. SQSTM1 expression level was significantly increased in HCC compared to the adjacent peritumor cirrhotic liver tissues (Z = 5.927, P < 0.001∗). Significant direct relation was found between SQSTM1 expression level in HCC and the pathological grade of the tumor (H = 33.789, P < 0.001∗). On follow-up, tumor and peritumor SQSTM1 expression levels performed significantly as a potential predictor of the overall survival, but not the disease recurrence.
Conclusions:
SQSTM1 expression could determine aggressive HCC, even with reasonable tumor size and number, and identify the subset of HCC patients with short overall survival and unfavorable prognosis. SQSTM1 expression could not predict post-RFA intrahepatic HCC recurrence. SQSTM1 may be a potential biomarker and target for the selection of HCC patients for future therapies.
Insights
Increased SQSTM1 protein in hepatocellular carcinoma (HCC) indicates aggressive disease and predicts shorter survival, but does not predict recurrence after radiofrequency ablation (RFA). SQSTM1 may guide future HCC therapies.
Area of Science:
- Cell Biology
- Oncology
- Gastroenterology
Background:
- Autophagy is crucial for cellular homeostasis, involving the degradation of cellular components via lysosomes.
- SQSTM1 is a key autophagy molecule implicated in signaling pathways, oxidative stress, and inflammation.
- Dysfunctional autophagy and SQSTM1 accumulation are linked to various diseases, including hepatocellular carcinoma (HCC).
Purpose of the Study:
- To investigate SQSTM1 protein expression in HCC.
- To correlate SQSTM1 levels with clinicopathological features of HCC.
- To assess the relationship between SQSTM1 expression and tumor recurrence after radiofrequency ablation (RFA).
Main Methods:
- Study included 50 patients with cirrhotic HCC eligible for RFA.
- Tumor and peritumor biopsies were analyzed for pathological grade and SQSTM1 expression via immunohistochemistry.
- Patients were followed for one year post-RFA to monitor for tumor recurrence.
Main Results:
- Serum alpha-fetoprotein and tumor pathological grade significantly correlated with RFA response.
- SQSTM1 expression was significantly elevated in HCC compared to adjacent cirrhotic liver tissue.
- Higher SQSTM1 levels in HCC directly correlated with increased tumor pathological grade.
- SQSTM1 expression predicted overall survival but not disease recurrence after RFA.
Conclusions:
- SQSTM1 expression identifies aggressive HCC and patients with poor prognosis.
- SQSTM1 expression does not predict intrahepatic HCC recurrence post-RFA.
- SQSTM1 may serve as a biomarker for selecting HCC patients for targeted therapies.
