Molecular features and gene expression signature of metastatic colorectal cancer (Review)

Abstract

Uncontrollable metastatic outgrowth process is the leading cause of mortality worldwide, even in the case of colorectal cancer. Colorectal cancer (CRC) accounts for approximately 10% of all annually diagnosed cancers and 50% of CRC patients will develop metastases in the course of disease. Most patients with metastatic CRC have incurable disease. Even if patients undergo resection of liver metastases, the 5-year survival rate ranges from 25 to 58%. Next-generation sequencing of tumour specimens from large colorectal cancer patient cohorts has led to major advances in elucidating the genomic landscape of these tumours and paired metastases. The expression profiles of primary CRC and their metastatic lesions at both the gene and pathway levels were compared and led to the selection of early driver genes responsible for carcinogenesis and metastasis-specific genes that increased the metastatic process. The genetic, transcriptional and epigenetic alteration encoded by these genes and their combination influence many pivotal signalling pathways, enabling the dissemination and outgrowth in distant organs. Therapeutic regimens affecting several different active pathways may have important implications for therapeutic efficacy.

Mutations in Homologous Recombination Repair Genes in Colorectal Cancer Are Associated With Favorable Response to Immune Checkpoint Inhibitors

“…Adjuvant treatments such as chemo-and radiotherapy have improved prognosis for patients with resectable tumors, but 40% of patients with stage II or III disease suffer recurrence within 5 years after surgery, and 20% of patients with resectable tumors develop metastases. In addition, about a quarter of patients are diagnosed when the disease is already at an advanced stage and has metastasized 4,5 . CRC shows considerable heterogeneity, which affects the disease course, response to treatment and prognosis.…”

Prognostic and immunological roles of Fc fragment of IgG binding protein in colorectal cancer

“…In addition, ~20% of patients with CRC present with distant metastases at the time of initial diagnosis ( 3 ). Despite notable advances in treatment strategies for CRC, such as surgery, chemotherapy and radiotherapy, >50% of patients with CRC develop metastasis, leading to a high mortality rate ( 4 , 5 ). Therefore, an improved understanding of the mechanisms underlying CRC pathogenesis is urgently needed to develop effective diagnostic and prognostic biomarkers and to identify potential therapeutic targets.…”

Clinical Impact of X-Ray Repair Cross-Complementary 1 (XRCC1) and the Immune Environment in Colorectal Adenoma–Carcinoma Pathway Progression

“…Colon cancer progression occurs through a well‑defined series of transformations from normal colonic epithelial cells to precursor adenoma lesions that eventually evolve into increasingly more invasive and malignant stages. 1 The following three molecular carcinogenesis pathways have been recognized: (1) chromosomal instability, 2 (2) microsatellite instability (MSI), 3 , 4 and (3) CpG island methylator phenotype. 5 Morphologically, this progression initially manifests as low-grade dysplasia (LGD) with the development of cytologic adenomatous dysplasia, and subsequent stepwise progression into high-grade dysplasia (HGD), ultimately leading to the development of colorectal cancer (CRC).…”