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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number962473
JournalFrontiers in Oncology
Volume12
DOIs
StatePublished - 20 Sep 2022

Keywords

  • Lynch syndrome
  • colon cancer
  • exosomes
  • genetic syndromes
  • telomerases

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