The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer

Eklöf, Vincy; Wikberg, Maria L.; Edin, Sofia; Dahlin, Anna M.; Jonsson, Bengt‐Gunnar; Öberg, Åke; Rutegård, Jörgen; Palmqvist, Richard

doi:10.1038/bjc.2013.212

Cited by 142 publications

(109 citation statements)

References 43 publications

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“…Given that there is increasing evidence the BRAFV600E mutant microsatellite stable tumours are a particularly poor prognostic group, [22][23][24][25][26][27][28] we attempted to further stratify mucinous MMRp tumours on the basis of BRAF status. Interestingly, and perhaps unexpectedly, we found similar 5-year survival rates for BRAF wild type (57%) and BRAFV600E mutant (51%) MMRp mucinous colorectal cancers (P = 0.610).…”

Section: Discussionmentioning

confidence: 99%

Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer

et al. 2016

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There is some uncertainty about pathological grading of mucinous colorectal adenocarcinoma, defined as colorectal cancer demonstrating at least 50% mucinous differentiation. Under the WHO 2000 classification mucinous colorectal cancer was considered high grade. However under the current WHO 2010 classification microsatellite unstable/mismatch repair-deficient (MSI/MMRd) mucinous colorectal cancer is considered low grade, whereas microsatellite stable/mismatch repair proficient (MSS/MMRp) tumours are high grade. However there is little empirical evidence for this approach. We therefore compared the long term survival of patients with MSI/MMRd vs MSS/MMRp mucinous colorectal cancer in a large unselected cohort of patients undergoing surgery at our institution from 1998 to 2011. There were 2608 patients in the cohort, of which 264 (10.1%) were mucinous. 95 (36%) of the mucinous tumours were microsatellite unstable. The all-cause 5-year survival of mucinous MSI/MMRd colorectal cancer was similar to that of non-mucinous low-grade colorectal cancer (73 vs 67%, P = 0.368), and significantly better than that of both non-mucinous high-grade (73 vs 53%, Po 0.001) and mucinous MSS/MMRp colorectal cancer (73 vs 57%, P = 0.023). The 5-year survival of mucinous MSS/MMRp colorectal cancer was slightly better than that of non-mucinous high-grade patients (57 vs 53%, P = 0.027), but significantly worse than that of non-mucinous low-grade colorectal cancer (57 vs 67%, P = 0.018). In multivariate Cox regression analysis, conventional histological grade based on glandular differentiation maintained prognostic significance (P = 0.003) whereas MSI/MMRd status just failed to be statistically significant (P = 0.062). Our findings support the WHO 2010 approach that as a group mucinous MSS/MMRp colorectal cancers are biologically aggressive. However, grading based exclusively on MSI/MMR status may be overly simplistic as conventional grading based on the degree of glandular differentiation still holds greater prognostic significance in multivariate analysis.

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Section: Discussionmentioning

confidence: 99%

Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer

et al. 2016

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“…Studies found that the incidence of BRAF mutations in right-sided colon cancer was increase compared with that in left-sided colon cancer [62,63]. Correlation meta-analysis revealed that BRAF mutation is a high risk factor for the prognosis of colon cancer [64]. The difference in genetic alterations between left-and the right-sided colon cancers should be further studied.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 96%

Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data

Liang

Zeng

Qin

et al. 2018

Cell Physiol Biochem

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Key WordsLeft-and right-sided • Colon cancer • Prognosis • TCGA Abstract Background/Aims: Left-and right-sided colon cancers are considered to be two different diseases and have altered outcomes. However, specific molecules to predict the prognosis of left-and right-sided colon cancers are currently lacking. Methods: Expression profiling of colon cancer were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) of left-and right-sided colon cancers were compared by DESeq analysis. The prognostic values of DEGs were assessed by univariate and multivariate Cox regression. Prognostic index models of two side colon cancers were conducted with prognostic values genes, respectively. Interaction of DEGs was then analyzed by the protein-protein interaction (PPI). Different biology function of two sides of colon cancer was assessed by Gene Set Enrichment Analysis (GSEA). Results: A total of 167 DEGs were identified between left-and right-sided colon cancers based on TCGA data. Using univariate COX regression analysis, five genes (PHACTR3, CKMT2, CYP2W1, ERFE, HOXC4) were related to overall survival in left-sided, and eight distinguishable genes (EREG, ERFE, HOXC6, SLC22A31, TFF1, GFI1, ZG16, RASL10B) in right-sided. Further, left-sided prognostic model was established with PHACTR3 and CKMT2 (HR=2.040; 95%CI=1.004-4.145; P=0.049). Distinguishable prognostic signature for right-sided colon cancer was established based on EREG, ERFE, GFI1, and RASL10B (HR=3.530; 95%CI: 1.934-6.444; P<0.001) in multivariate analysis. PPI analysis of 167 DEGs showed that CCL5, GNG4, GNLY, GZMH, DRD2, and FASLG genes were at the core of interaction network. In GSEA function analysis, four pathways, including antigen processing and presentation, natural killer cell mediated cytotoxicity, intestinal immune network for Iga production, and type I diabetes mellitus, were significantly enriched in the DEGs of the right-sided colon cancer. Conclusions: This study constructs a panel of potential prognostic model of left-and right-sided colon cancers, respectively. We also provide molecular biological alterations between left-and rightsided colon cancers.

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“…BRAF mutations, specifically V600E, which occur in less than 10% of patients with metastatic CRC, are associated with a poor prognosis (Richman et al, 2009;Van Cutsem et al, 2011). PIK3CA mutations are found in about 15% of CRC patients, and occur mainly in exon 9 and exon 20 (Roock et al, 2010;Garrido-Laguna et al, 2012), but their role as a biomarker of resistance to chemotherapy remains controversial (Mao et al, 2012;Eklöf et al, 2013). Thus, mutations in these genes may affect the prognosis of patients with PC from CRC.…”

Section: Introductionmentioning

confidence: 99%

Value of KRAS, BRAF, and PIK3CA Mutations and Survival Benefit from Systemic Chemotherapy in Colorectal Peritoneal Carcinomatosis

Sasaki¹,

Hamaguchi²,

Yamada³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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. Among all patients, tumor location, number of metastatic sites and BRAF mutation status were significant prognostic factors, whereas the presence of PC was not. In the PC group, chemotherapy with bevacizumab resulted in a significantly longer OS than forchemotherapy without bevacizumab (HR=0.38, p<0.01), but this was not the case in the non-PC group (HR=0.80, p=0.10). Furthermore, the incidence of the BRAF V600E mutation was significantly higher in PC than in non-PC patients (27.7% versus 7.3%, p<0.01). BRAF mutations displayed a strong correlation with shorter OS in non-PC (HR=2.26), but not PC patients (HR=1.04). Conclusions: Systemic chemotherapy, especially when combined with bevacizumab, improved survival in patients with PC from CRC as well as non-PC patients. While BRAF mutation demonstrated a high frequency in PC patients, but it was not associated with prognosis.

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The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer

Cited by 142 publications

References 43 publications

Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer

Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer

Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data

Value of KRAS, BRAF, and PIK3CA Mutations and Survival Benefit from Systemic Chemotherapy in Colorectal Peritoneal Carcinomatosis

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