Biomarkers in colorectal cancer: Current clinical utility and future perspectives

Abstract

Colorectal cancer (CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a sporadic disease in most cases (75%-80%), but it has been suggested that crosstalk between gene mutations (i.e., mutations of BRAF, KRAS, and p53 as well as microsatellite instability) and epigenetic alterations (i.e., DNA methylation of CpG island promoter regions) could play a pivotal role in cancer development. A number of studies have focused on molecular testing to guide targeted and conventional treatments for patients with CRC, sometimes with contrasting results. Some of the most useful innovations in the management of CRC include the possibility to detect the absence of KRAS, BRAF, NRAS and PIK3CA gene mutations with the subsequent choice to administer targeted adjuvant therapy with anti-epidermal growth factor receptor antibodies. Moreover, CRC patients can benefit from tests for microsatellite instability and for the detection of loss of heterozygosity of chromosome 18q that can be helpful in guiding therapeutic decisions as regards the administration of 5-FU. The aim of this review was to summarize the most recent evidence on the possible use of genetic or epigenetic biomarkers for diagnosis, prognosis and response to therapy in CRC patients.

Genomic Profiling of Stage II Colorectal Cancer Identifies Candidate Genes Associated with Recurrence-Free Survival, Tumor Location, and Differentiation Grade

“…Our results confirm the association between BRAF mutation and age at diagnosis, with tumor location in colon [37,39,40], and with poor tumor differentiation in CRC stage II [36,41]. The observed association between KRAS and a higher degree of tumor differentiation has been described both in CRC stage II and III [35].…”

Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy

“…The identification of biomarkers that associate or predict the benefit of an appropriate selection of patient candidates for both 5-FU-based and combined therapies constitutes a broad area useful in clinical and translational research of CRC disease. However, the low specificity of chemotherapy and the great heterogeneity of the patients and samples analysed make the search for predictive biomarkers very complex [2]. Tests for microsatellite instability (MSI) and for the detection of loss of heterozygosity for chromosome 18q (18qLOH) in the early stage of the disease are beginning to be evaluated for guiding therapeutic decisions regarding the administration of 5-FU-based treatments; however, these are still under investigation.…”

<p>Matrix Stiffness and Colorectal Cancer</p>

“…Mutations in genes initiate the process of colon cancer, and previous studies have focused on the biochemical aspects of colon cancer cells. 7,8 The role of biomechanics in tumorigenesis has been underestimated. With the development of methodology in colon cancer research, people gradually realized the indispensable role of mechanical factors in the progression of colorectal cancer.…”