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Telomerase as Biomarker in Colorectal Cancer

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Biomarkers in Cancer

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, with over one million new cases every year. Although improved treatments, increased awareness, and early detection have contributed to prolonged survival, CRC still represents an important cause of cancer-related deaths. CRC is a heterogeneous complex of diseases differing in molecular pathways and biological characteristics, arising through a multistep process; this molecular and biological heterogeneity also accounts for the great clinical variability of the disease. The management of CRC requires a multimodal approach, and many efforts have been made to identify molecular markers able to predict the outcome of CRC patients.

Telomerase is a ribonucleoprotein complex containing the catalytic protein telomerase reverse transcriptase (TERT) with telomere-specific reverse transcriptase activity which synthesizes telomere sequences utilizing an internal RNA template. The maintenance of telomere length by telomerase is critical to preserving the replicative potential of cancer cells. Several pieces of evidence suggest that TERT, besides its capacity to extend telomeres, is also involved in other cellular functions, including activation of proliferative signaling pathways and antiapoptotic activity, even by telomere-length-independent mechanisms. In view of its critical role in the oncogenetic process, telomerase may be a molecular marker of neoplastic disease.

The aim of this chapter is to analyze literature data in order to assess the role of telomerase expression and/or activity in the carcinogenesis of colorectal cancer and its value as a prognostic marker of disease progression. The potential use of circulating TERT as a biomarker for minimally invasive monitoring of the disease and response to therapy is also discussed.

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Abbreviations

APC:

Adenomatous Polyposis Coli

CIN:

Chromosomal Instability

CRC:

Colorectal Cancer

CRT:

Chemoradiotherapy

DCC:

Deleted in Colorectal Carcinoma

DFS:

Disease-Free Survival

EGFR:

Epidermal Growth Factor Receptor

FU:

Fluorouracil

GAPDH:

Glyceraldehyde-3-Phosphate Dehydrogenase

HIF:

Hypoxia-Inducible Factor

HPRT1:

Hypoxanthine Phosphoribosyltransferase 1

MAPK:

Mitogen-Activated Protein Kinase

MMR:

Mismatch Repair System

MSI:

Microsatellite Instability

MSS:

Microsatellite Stable

OS:

Overall Survival

PCR:

Polymerase Chain Reaction

TERT:

Telomerase Reverse Transcriptase

TRAP:

Telomere Repeat Amplification Protocol

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Bertorelle, R., De Rossi, A. (2015). Telomerase as Biomarker in Colorectal Cancer. In: Preedy, V., Patel, V. (eds) Biomarkers in Cancer. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7681-4_2

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