Clinical utility of telomeres as diagnostic and short-term prognostic markers in loco-regional treatment of hepatocellular carcinoma.
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BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with high mortality at advanced stages. Loco-regional treatment including: Radiofrequency (RF) or transarterial chemoembolization (TACE) is decided according to the size, and the site of the tumor, according to practice guidelines. Alpha fetoprotein (AFP), the most used biomarker in the guidelines, although specific, lacks sensitivity. New biomarkers are needed to understand the underlying pathophysiology, and to be used in clinical practice. AIM: To study the effect of loco-regional treatment on telomere length, as a diagnostic and short-term (3 months) prognostic marker. METHODS: This is a prospective cohort study, and includes 60 patients visiting Ain Shams University Hospitals. The patients were divided into 2 groups: 30 patients with liver cirrhosis (group 1) and 30 HCC patients undergoing RF or TACE (group 2). Laboratory investigations for all patients included: Telomere length in peripheral leukocytes by polymerase chain reaction, AFP, and liver function. In the HCC group, the aforementioned laboratory investigations with abdominal triphasic computed tomography with contrast were performed at baseline, and after 3 months. RESULTS: With regard to age, Child-Pugh and Model for End-Stage Liver Disease scores, there was no statistically significant correlation with telomere length. However, there was a correlation between telomere length and age, and both scores before and after 3 months of treatment among HCC patients. On dividing the HCC group according to tumor size with a cutoff of 5 cm, and performing the Mann-Whitney test we found that at baseline telomere length was significantly lower among cases with tumor size ≥ 5 cm than in those with tumor size < 5 cm (30 patients; P = 0.03). In addition, we found a positive Spearman's rank correlation between telomere length and tumor size in the ≥ 5 cm only group (28 samples from the before and after intervention data; P = 0.025). CONCLUSION: Telomere length in leukocytes is a potential marker in HCC tumor prognosis. Further research using telomerase activity and telomerase reverse transcriptase promoter gene mutation in a larger cohort is recommended.