Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review)

Abstract

Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer‑related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).

Figure 1.

Steps of CRC progression and a summarized rendering of the pathogenetic model. CRC, colorectal cancer; APC, adenomatous polyposis coli.

Figure 2.

A graphic overview of the current and potential biomarkers used in CRC. CRC, colorectal cancer; CDX2, caudal type homeobox 2; CEA, carcinoembryonic antigen; CIN, chromosomal instability; MSI, microsatellite instability; CIMP, CpG island methylation phenotype; APC, adenomatous polyposis coli; ctDNA, circulating tumor DNA; miRNA, microRNA; SATB2, special AT-rich sequence binding protein 2; CK, cytokeratin; VEGF, vascular endothelial growth factor; IMP3, insulin-like growth factor-II mRNA-binding protein 3; TNIK, Traf2- and Nck-interacting kinase; BRAF, B-rapidly accelerated fibro-sarcoma (proto-oncogene); MSI, microsatellite instability; CA 19-9, cancer antigen 19-9; CTCs, circulating tumor cells; PI3K, phosphoinositide 3-kinase; MN, micronuclei.

Figure 3.

Wnt/β-catenin signaling pathway. When Wnt is present, it binds to FzR and LRP5 receptor. Dsh enables the phosphorylation of GSK-3β and CK1, resulting in the binding of axin. Following to accumulation of β-catenin and translocation to the nucleus, it binds to various factors in order to modulate the transcription of target-genes. These processes lead to antiapoptotic results and promote cellular proliferation. FzR, frizzled receptor; LRP5, low-density lipoprotein receptor-related protein 5; GCSK3-β, glycogen-synthase kinase 3β; CK1, casein kinase 1; ZNRF3, zinc and ring finger 3; APC, adenomatosis polyposis coli; Pygo, pygopus; Bcl9, B-cell CLL/lymphoma 9; Ep300, E1A binding protein p300; Tcf, T-cell factor; Lef, lymphoid enhancer-binding factor 1.

Figure 4.

The connection between chronic inflammation and development of CRC. CRC, colorectal cancer; GFs, growth factors; Il-1β, interleukin 1β; NF-κΒ, nuclear factor κB; HIF-1α, hypoxia inducible factor-1α; VEGF, vascular endothelial growth factor.

Figure 5.

Intracellular signals for CRC manifestation via EGFR. CRC, colorectal cancer; EGFR, epidermal growth factor receptor; BRAF, B-rapidly accelerated fibrosarcoma (proto-oncogene); MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase; S6K1, ribosomal protein S6 kinase β-1; PKB, protein kinase B; mTOR, mechanistic target of rapamycin.