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

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

doi:10.3389/fonc.2022.962473

Cited by 3 publications

(4 citation statements)

References 32 publications

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“…Our results suggest that the proportion of high levels of circulating telomerase transcript correlate with the extent of tumor malignancy and might serve as an indicator of oncogenic activity. These findings are in line with previous publications showing a similar phenomenon of increasing presence of circulating hTERT transcript with increasing tumor grade in both colorectal cancer 22 and hepatocellular carcinoma (in preparations). Furthermore, our findings in meningiomas and glioblastomas suggest that it also has the potential to serve as a clinical biomarker.…”

Section: Discussionsupporting

confidence: 93%

Is serum‐derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study

Uziel,

Kanner,

Beery

et al. 2023

Cancer Medicine

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BackgroundIn order to proliferate indefinitely, all tumors require a telomere maintenance mechanism. The expression of human telomerase reverse transcriptase (hTERT) enables telomere maintenance and provides cancer cells with limitless replicative potential. As such, it may serve as an attractive biomarker for oncogenic activity. This study explored whether a liquid biopsy that analyses blood derived exosomal hTERT transcript (e‐hTERT‐trans) may serve as such a biomarker in gliomas and meningiomas when compared to healthy controls.MethodsExosomes were isolated from the pre‐operative sera of patients' samples stored in the biobank of both Rabin and Sheba Medical Centers. The levels of e‐hTERT‐trans were measured in 81 healthy controls, 117 meningiomas, 17 low‐grade gliomas, and 61 glioblastomas. Clinical parameters of the patients were collected retrospectively and compared to the levels of the e‐hTERT‐trans.ResultsThe upper normal limit of controls e‐hTERT‐trans was 1.85 relative quantitation (RQ). The rate of detection increased with rising tumor grade and correlated with tumor recurrence in meningiomas: mean RQ without recurrence (2.17 ± 11.7) versus with recurrence (3.59 ± 4.42; p = 0.002). In glioblastomas, preoperative measurements correlated with tumor volume and with the disease course on serial sampling.ConclusionsWe demonstrated for the first time that the expression of e‐hTERT‐trans transcript can be measured in the serum of primary brain tumors. This exosomal marker carries the potential to serve as a biomarker once used in conjunction with other clinical and radiological parameters. Future studies are required to investigate whether the sensitivity could be augmented and whether it can be implemented into routine patients care.

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Section: Discussionsupporting

confidence: 93%

Is serum‐derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study

Uziel,

Kanner,

Beery

et al. 2023

Cancer Medicine

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“…Likewise, the levels of the hTERT transcript were correlated with levels of carcinoembryonic antigen (PSA) in patients with colorectal cancer and significantly differed from those of patients with polyps that served as a control group. In this study, we also measured the levels of the hTERT transcript in patients with Lynch syndrome, which is associated with a predisposition to colorectal cancer, and found positive levels of hTERT transcripts in several carriers [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy

et al. 2023

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Background: Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals. We sought to evaluate the feasibility of measuring serum exosomal hTERT transcripts levels in patients with lung cancer. Methods: A prospective analysis of exosomal hTERT mRNA levels was determined in serum-derived exosomes from 76 patients with stage III–IV lung cancer (11 SCLC and 65 NSCLC). An hTERT level above RQ = 1.2 was considered “detectable” according to a previous receiver operating characteristic curve (ROC) curve. Sequential measurements were obtained in 33 patients. Demographic and clinical data were collected retrospectively from patients’ charts. Data on response to systemic therapy (chemotherapy, immunotherapy, and tyrosine kinase inhibitors) were collected by the treating physicians. Results: hTERT was detected in 53% (40/76) of patients with lung cancer (89% of SCLC and 46% of NSLCC). The mean hTERT levels were 3.7 in all 76 patients, 5.87 in SCLC patients, and 3.62 in NSCLC patients. In total, 25 of 43 patients with sequential measurements had detectable levels of hTERT. The sequential exosomal hTERT mRNA levels reflected the clinical course in 23 of them. Decreases in hTERT levels were detected in 17 and 5 patients with partial and complete response, respectively. Eleven patients with a progressive disease had an increase in the level of exosomal hTERT, and seven with stable disease presented increases in its exosomal levels. Another patient who progressed on the first line of treatment and had a partial response to the second line of treatment exhibited an increase in exosomal hTERT mRNA levels during the progression and a decrease during the response. Conclusions: Exosomal hTERT mRNA levels are elevated in over half of patients with lung cancer. The potential association between hTERT levels and response to therapy suggests its utility as a promising cancer biomarker for response to therapy. This issue should be further explored in future studies.

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“…In fact, the identification of hTERT transcripts in the plasma of CRC patients may serve as a useful tool for disease monitoring, as mRNA levels correlate with those found in tumors [ 208 ]. The prognostic and predictive significance of cell-free circulating hTERT has been evaluated in CRC patients in detail [ 207 , 209 , 210 ]. Bertorelle et al showed that stage II CRC patients with lower levels of hTERT had better OS, while its presence at higher levels was correlated with a poor response to chemotherapy (as an independent prognostic factor) and with a higher risk of disease recurrence and death [ 207 ].…”

Section: Telomerase Activity and Crcmentioning

confidence: 99%

“…It has been shown that a variety of both normal and neoplastic cells can secrete them (among which are CRC cells) into the microenvironment from where they enter the bloodstream. Exosomes offer the advantage that their mRNA content is not exposed to the activity of extracellular RNases, allowing for reliable estimation [ 210 ]. In summary, ample evidence supports telomerase as a useful marker for monitoring and predicting outcomes in CRC [ 207 ].…”

Section: Telomerase Activity and Crcmentioning

confidence: 99%

Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy

Nikolouzakis,

Chrysos,

Docea

et al. 2024

Cancers

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Cancer of the colon and rectum (CRC) has been identified among the three most prevalent types of cancer and cancer-related deaths for both sexes. Even though significant progress in surgical and chemotherapeutic techniques has markedly improved disease-free and overall survival rates in contrast to those three decades ago, recent years have seen a stagnation in these improvements. This underscores the need for new therapies aiming to augment patient outcomes. A number of emerging strategies, such as immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), have exhibited promising outcomes not only in preclinical but also in clinical settings. Additionally, a thorough appreciation of the underlying biology has expanded the scope of research into potential therapeutic interventions. For instance, the pivotal role of altered telomere length in early CRC carcinogenesis, leading to chromosomal instability and telomere dysfunction, presents a promising avenue for future treatments. Thus, this review explores the advancements in CRC immunotherapy and telomere-targeted therapies, examining potential synergies and how these novel treatment modalities intersect to potentially enhance each other’s efficacy, paving the way for promising future therapeutic advancements.

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

Cited by 3 publications

References 32 publications

Is serum‐derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study

Is serum‐derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study

Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy

Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy

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