Meta-analysis of the molecular associations of mucinous colorectal cancer

Abstract

Background: Mucinous differentiation occurs in 5-15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer.Methods: This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis.Results: Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1⋅46, 95 per cent c.i. 1⋅08 to 2⋅00, P = 0⋅014) and BRAF (OR 3⋅49, 2⋅50 to 4⋅87; P < 0⋅001) mutation, MSI (OR 3⋅98, 3⋅30 to 4⋅79; P < 0⋅001) and CIMP (OR 3⋅56, 2⋅85 to 4⋅43; P < 0⋅001), and negatively with altered p53 expression (OR 0⋅46, 0⋅31 to 0⋅67; P < 0⋅001). Conclusion:The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.

Surgery improves the prognosis of colon mucinous adenocarcinoma with liver metastases: A SEER-Based Study

“…According to the WHO, MC is de ned as more than 50% of the lesion is composed of extracellular mucin. The molecular characteristics of MC are relative high mutation of BRAF and KRAS, more microsatellite instability high (MSI-H) and CpG island methylator phenohype, and high expression of HATH1 and MUC2 compared with AC [9][10][11]. The pathogenesis for MC is rarely known, bacterial bio lms, in ammatory bowel diseases (IBD) and radiotherapy are considered as potential risk factors [12,13].…”

“…The pathogenesis for MC is rarely known, bacterial bio lms, in ammatory bowel diseases (IBD) and radiotherapy are considered as potential risk factors [12,13]. MC is frequently located in proximal colon and had shorter survival and poorer systemic treatment response compared with AC, thus is always suggested as a poor prognostic predictor for CC [9,[14][15][16]. Therefore, we should pay more attention in clinical management of MC patients.…”

Surgery improves the prognosis of colon mucinous adenocarcinoma with liver metastases: A SEER-Based Study

“…According to the WHO, MC is de ned as more than 50% of the lesion being composed of extracellular mucin. The molecular characteristics of MC are a relatively higher mutation rate of BRAF and KRAS, a greater proportion of the microsatellite instability high (MSI-H) and CpG island methylator phenotype, and greater expression of HATH1 and MUC2 than AC [9][10][11]. The pathogenesis of MC is poorly understood, and bacterial bio lms, in ammatory bowel diseases (IBDs) and radiotherapy are considered as potential risk factors [12,13].…”

Mucinous adenocarcinoma of the colon and rectum: A genomic analysis

“…Some studies have attempted to unravel the genetic etiology of mucinous adenocarcinoma of the colon and rectum by predominantly focusing on mutations in Kirsten rat sarcoma viral oncogene ( KRAS) , v‐Raf murine sarcoma viral oncogene homolog B ( BRAF ), inherited defects or epigenetic silencing of mismatch repair (MMR) proteins resulting in microsatellite instability (MSI) and the presence of the CpG island methylator phenotype (CIMP) . Mucinous tumors have been shown to be associated with an increased rate of BRAF mutations, MSI and CIMP and negatively associated with altered TP53 expression but little else has been described about the genetic mechanisms of these tumors beyond this . This study provides a more in‐depth explanation of the genomic aberrations in mucinous adenocarcinoma by focusing on a greater number of genes and by providing analyses on copy number alteration (CNA) and oncogenic signaling pathways in an attempt to discern the molecular mechanisms driving the mucinous phenotype.…”

“…[10][11][12][13][14][15][16] Mucinous tumors have been shown to be associated with an increased rate of BRAF mutations, MSI and CIMP and negatively associated with altered TP53 expression but little else has been described about the genetic mechanisms of these tumors beyond this. 17 This study provides a more in-depth explanation of the genomic aberrations in mucinous adenocarcinoma by focusing on a greater number of genes and by providing analyses on copy number alteration (CNA) and oncogenic signaling pathways in an attempt to discern the molecular mechanisms driving the mucinous phenotype.…”