AUTHOR=Laish Ido , Levi Zohar , Mahajna Hussein , Albshesh Ahmad , Horesh Nir , Katz Efraim , Feldman Dan , Shinar Nadav , Picard Orit , Yavzori Miri , Fudim Ella , Raanani Pia , Berger Tamar , Goldvaser Hadar , Beery Einat , Uziel Orit 

TITLE=Characterization of blood-derived exosomal hTERT mRNA as a biomarker for colon cancer and Lynch syndrome

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.962473

DOI=10.3389/fonc.2022.962473

ISSN=2234-943X

ABSTRACT=Background: Human telomerase reverse transcriptase (hTERT)- mRNA was shown to be elevated in exosomes derived from the sera of a variety of hematological and solid cancer patients. We aimed to evaluate its role as a diagnostic marker in patients with newly diagnosed colon cancer and in hereditary syndromes with predisposition to colon cancer.  
Methods:  hTERT -mRNA levels were determined in serum-derived exosomes from
88 patients with colon cancer, 71 Lynch-syndrome carriers with unknown active malignancies and 50 healthy controls. Data, including demographics, background diseases, clinical data regarding tumor characteristics and genetic data, were retrieved data from medical files. 
Results: Patients with colon cancer had both higher exosomal hTERT mRNA levels and a higher proportion of patients with positive exosomal hTERT mRNA than controls (29.5% vs. 4%, respectively, P values < 0.001). Within the cancer group, patients with a metastatic disease had higher levels of telomerase mRNA than non-metastatic disease patients, and these levels correlated with CEA levels. Likewise, Lynch syndrome carriers had a higher proportion of positive exosomal hTERT mRNA than controls (21.1% vs. 4%, respectively, P value 0.008) but only a trend towards higher exosomal hTERT mRNA levels. Higher telomerase mRNA levels were not correlated with the mutated gene. 
Conclusions:  Exosomal serum hTERT –mRNA levels are associated with metastatic colon cancer and were also demonstrated in a subset of Lynch syndrome carriers. Its significance as a biomarker for developing malignancy should be elucidated.