Colorectal cancer: epigenetic alterations and their clinical implications

Abstract

Colorectal cancer (CRC) is a heterogeneous disease with distinct molecular and clinical features, which reflects the wide range of prognostic outcomes and treatment responses observed among CRC patients worldwide. Our understanding of the CRC epigenome has been largely developed over the last decade and it is now believed that among thousands of epigenetic alterations present in each tumor, a small subgroup of these may be considered as a CRC driver event. DNA methylation profiles have been the most widely studied in CRC, which includes a subset of patients with distinct molecular and clinical features now categorized as CpG island methylator phenotype (CIMP). Major advances have been made in our capacity to detect epigenetic alterations, providing us with new potential biomarkers for diagnostic, prognostic and therapeutic purposes. This review aims to summarize our current knowledge about epigenetic alterations occurring in CRC, underlying their potential future clinical implications in terms of diagnosis, prognosis and therapeutic strategies for CRC patients.

Association of the prognostic nutritional index and overall survival in patients with colorectal cancer: A STROBE compliant retrospective cohort study

“…Most frequently evaluated prognostic factors include those directly associated to the neoplasm per se, that is, morphologic, proteomic, genomic or epigenomic, while the patient's immune and nutritional status have been often overlooked . There is an increasing evidence that systemic inflammation plays a critical role in carcinogenesis and the invasion or metastatic processes in CRC .…”

“…22 Most frequently evaluated prognostic factors include those directly associated to the neoplasm per se, that is, morphologic, proteomic, genomic or epigenomic, while the patient's immune and nutritional status have been often overlooked. [6][7][8][9] There is an increasing evidence that systemic inflammation plays a critical role in carcinogenesis and the invasion or metastatic processes in CRC. 30 The tumor-associated inflammatory response has been recognized to exert a contradictory effect, enhancing tumorigenesis and progression, and actually aiding incipient neoplasms to acquire hallmark capabilities.…”

“…However, OS cannot be completely explained by TNM stages or by the currently established prognostic factors . In CRC, several prognostic factors improving the prognostic value of the TNM classification have been described . However, more refined tools are needed to further increase their prognostic value.…”

“…4 In CRC, several prognostic factors improving the prognostic value of the TNM classification have been described. [5][6][7] However, more refined tools are needed to further increase their prognostic value. The Memorial Sloan-Kettering Cancer Center model, which was designed to predict the 5-and 10-year disease-free survival after curative resection in patients with colon cancer, or the European CanCer Organisation/European Society of Surgical Oncology nomograms predicting recurrence, distant metastases and OS, 8,9 have been important contributions to the field.…”

miR-135a Protects Dextran Sodium Sulfate-Induced Inflammation in Human Colorectal Cell Lines by Activating STAT3 Signal

“…Although the pathological mechanisms are multifactorial, such as environmental, genetic, immune mediated, and gut microbial factors, the main targets of therapy focus on colonic inflammation [1,3,4]. Cytokines play an important role in the pathogenesis of IBD by mediating multiple aspects of the inflammatory response [5][6][7][8].…”