Detection of serum levels of human telomerase reverse transcriptase mRNA in non-alcoholic steatohepatitis related hepatocellular carcinoma in Sri Lanka

Objectives: A key driver gene implicated in hepatocellular carcinoma (HCC) is the upregulation of human telomerase reverse transcriptase ( hTERT ). Non-alcoholic steatohepatitis - related hepatocellular carcinoma (NASH-HCC) has emerged as one of the most prevalent HCC subtypes. However, studies on the clinical impact of hTERT expression levels from NASH-HCC patients in Sri Lanka are scarce. This study aimed to evaluate the serum levels of hTERT mRNA in patients with NASH-HCC in comparison to cirrhotic age, body mass index (BMI), and gender matched controls, and analyse the possible link between the hTERT mRNA expression levels and descriptive, clinical and tumour characteristics data of NASH-HCC patients. Material and Methods: Twenty - one participants were recruited, including 7 NASH-HCC test subjects, 7 cirrhotic age, BMI and gender matched controls and 7 healthy controls. mRNA extracted; cDNA was prepared using kit protocols with minor optimisations, while qPCR was run with the SYBR green method. Statistical Package for Social Science (SPSS) version 20 was used for the analysis, and data were presented as mean ± standard deviation (SD). Mann- Whitney U test was used to analyse the differences in hTERT mRNA between the NASH-HCC and cirrhotic matched-controls. Spearman’s rho test was used to evaluate the correlation between the hTERT mRNA levels and the descriptive, clinical, and tumour characteristics data. The p -value for all analyses was considered statistically significant if <0.05. Results: The analysis revealed a markedly elevated expression of hTERT mRNA in the NASH-HCC cohort, with a mean level of 9.11 ± 8.44, representing a sevenfold increase compared to the cirrhotic matched control cohort, which exhibited a mean expression level of 1.3 ± 1.49. Among the correlated parameters, only alanine aminotransferase (ALT) and tumour nodularity correlated with hTERT mRNA expression from NASH-HCC patients, suggesting a possible link between hTERT activity and disease severity. Conclusion: The significantly higher serum expression of hTERT in NASH-HCC patients, coupled with correlated ALT and tumour nodularity, signified its potential as a diagnostic biomarker for NASH-HCC. Further studies are recommended to evaluate the further link between hTERT mRNA expression levels and some of its genetic driving risk factors, such as pathogenic hTERT promoter SNPs and related transcription factors, using a larger sample size.