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=12 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.