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Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2025; 31(46): 112530
Published online Dec 14, 2025. doi: 10.3748/wjg.v31.i46.112530
Clinical utility of telomeres as diagnostic and short-term prognostic markers in loco-regional treatment of hepatocellular carcinoma
Sarah El-Nakeep, Hossameldin AbdelAziz, Tari George Michael, Ahmed Mohamed ElGhandour, Hoda A Abdelsattar, Fatma Mohamed Rafat Awad, Anup Kasi
Sarah El-Nakeep, Hossameldin AbdelAziz, Tari George Michael, Ahmed Mohamed ElGhandour, Fatma Mohamed Rafat Awad, Hepatogastroenterology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
Hoda A Abdelsattar, Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
Anup Kasi, Department of Gastrointestinal Oncology, University of Kansas Cancer Center, Westwood, KS 66205, United States
Author contributions: El-Nakeep S, AbdelAziz H, Abdelsattar HA, and Kasi A designed the research study; Michael TG, ElGhandour AM, Abdelsattar HA and Awad FR performed the research; Abdelsattar HA and Awad FR contributed new reagents and analytic tools; El-Nakeep S, ElGhandour AM, Abdelsattar HA, and Kasi A analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: This study was approved by the Research Ethics Committee (REC), Faculty of Medicine, Ain Shams University, Cairo, Egypt, approval No. FMASU MD 11/2021.
Informed consent statement: All patients signed an informed consent before starting the study.
Conflict-of-interest statement: All authors declare that there is no conflict of interest.
Data sharing statement: All data in this study are available upon reasonable request from the authors.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sarah El-Nakeep, MD, Professor, Hepatogastroenterology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ramsses Street, Abassyia Square, Cairo 11736, Egypt. sarahnakeep@gmail.com
Received: July 30, 2025
Revised: September 23, 2025
Accepted: October 23, 2025
Published online: December 14, 2025
Processing time: 133 Days and 8.8 Hours
Abstract
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.

Keywords: Hepatocellular carcinoma; Telomeres; Telomere length; Telomerase; Transarterial chemoembolization; Radiofrequency; Loco-regional therapy; Diagnosis; Prognosis

Core Tip: We examined the telomere length in peripheral leukocytes, as a biomarker for diagnosis and short-term prognosis of loco-regional therapy in hepatocellular carcinoma (HCC). We found that in patients with HCC or chronic liver disease, the telomere length is short. When we used a cutoff of 5 cm it was found that in patients with larger tumors, the telomere length was shorter. Moreover, in large tumors the telomere length increased, as the size of the tumor increased. This is the first study to include Egyptian patients. We hope this study paves the way for further research on telomeres in HCC prognosis, and diagnosis.