Novel Prognostic Biomarkers in Metastatic and Locally Advanced Colorectal Cancer: Micronuclei Frequency and Telomerase Activity in Peripheral Blood Lymphocytes.

Taxiarchis Konstantinos Nikolouzakis,John Souglakos,Polychronis D Stivaktakis,Athanasios Alegakis,Aikaterini Berdiaki,Elena Vakonaki,Nikolaos Razos,John Tsiaoussis,Aristidis Tsatsakis

doi:10.3389/fonc.2021.683605

Taxiarchis Konstantinos Nikolouzakis, John Souglakos + Show 7 more

Open Access

https://doi.org/10.3389/fonc.2021.683605

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Abstract

PurposeDue to the current practice on colorectal cancer (CRC) management, chemoresistance is most often recognized at the end of the treatment. Therefore, effective and easy-to-use prognostic biomarkers are needed.Experimental DesignWe evaluated the prognostic significance of two novel CRC biomarkers: a) micronuclei frequency (MNf) in 55 metastatic CRC (mCRC) and 21 locally advanced rectal cancer (laRC) patients using cytokinesis block micronucleus assay (CBMN assay) and b) telomerase activity (TA) in 23 mCRC and five laRC patients using TRAP-ELISA. Both biomarkers were evaluated in peripheral blood lymphocytes (PBLs) before, at the middle, and at the end of the therapy (approximately 0, 3, and 6 months) for mCRC patients before, at the end of the therapy, and after surgery for laRC patients.ResultsOverall, MNf demonstrated significant prognostic value since a decrease of MNf less than 29% between middle and initial MNf measurements can discriminate between progressive and stable/responsive disease with sensitivity of 36% and specificity of 87.0% while being able to identify responsive disease with sensitivity of 72.7% and specificity of 59.3%. On the other hand, TA presented a significant trend of increase (p = 0.07) in patients with progressive disease at the middle measurement.ConclusionsThe findings of this study suggest that the MN frequency may serve as a promising prognostic biomarker for the monitoring of the treatment response of patients with CRC, while TA should be evaluated in a larger group of patients to further validate its significance.

Highlights

Colorectal cancer is considered as one of the leading causes of cancer-related morbidity and mortality worldwide for both sexes
Inclusion criteria were: I) Patients with radiologic evidence of mCRC documented by computed tomography (CT) and/or magnetic resonance imaging (MRI) presenting measurable disease treated with first line systemic treatment according to the Hellenic Society of Medical Oncologists (HeSMO) guidelines [20], II) Patients with radiologic evidence of laRC, documented by abdominal and chest CT and abdominal and pelvic MRI presenting measurable disease and receiving induction chemotherapy according to the Hellenic Society of Medical Oncologists (HeSMO) guidelines [21]
In our mCRC group, 29 patients were treated with FOLFOX, 22 with FOLFIRI, and four with FOLFOXIRI (52.7, 40, and 7.3% respectively), while 40 patients received an additional treatment with a biological agent based on their genetic profile; 19 were treated with bevacizumab, five with aflibercept, nine with cetuximab, and seven with panitumumab (34.5, 9, 16.3, and 12.7% )

Summary

Introduction

Colorectal cancer is considered as one of the leading causes of cancer-related morbidity and mortality worldwide for both sexes. Patients with complete or partial response had further decrease in MNf at the end of the treatment in contrast to those with stable or progressive disease This finding suggests that a decrease of cancer load can be identified by the concomitant decrease of MNf, while an increase of the cancer load (due to the emergence of a chemoresistant cluster of cancer-cells) will result in an increase of MNf, but not to the same level as before treatment. Our team focused on validating the clinical and possible prognostic value of two novel biomarkers (MNf and TA) for laCRC and mCRC These biomarkers were chosen on the basis of their close relation to chromosomal instability (CIN) and aberrant genetic function, both major hallmarks in colorectal carcinogenesis [6]

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