Molecular subtyping improves prognostication of Stage 2 colorectal cancer

Purcell, Rachel; Schmeier, Sebastian; Lau, Yee Chen; Pearson, John F.; Frizelle, F. A.

doi:10.1186/s12885-019-6327-4

Cited by 16 publications

(15 citation statements)

References 35 publications

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“…Moreover, patients with MSI and CMS1 have a better OS and RFS compared to CMS2-4. Contrary to previous results, Purcell et al [ 39 ] reported that stage II patients with CMS3 had a worse prognosis in OS than patients in CMS1-2, although an imbalance between CMS groups, with few CMS4 patients, could explain this result. Besides the possibility for CMS to determine CRC subtypes with worse prognosis for proposing personalized treatments, CMS still needs more studies to define the differences in the prognosis of patients through the different TNM stages of CRC.…”

Section: Cms and Prognosiscontrasting

confidence: 63%

Consensus molecular subtypes of colorectal cancer in clinical practice: A translational approach

Valenzuela¹,

Canepa²,

Simonetti³

et al. 2021

WJCO

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The identification of several genetic mutations in colorectal cancer (CRC) has allowed a better comprehension of the prognosis and response to different antineoplastic treatments. Recently, through a systematic process, consensus molecular subtypes (CMS) have been described to characterize genetic and molecular mutations in CRC patients. Through CMS, CRC patients can be categorized into four molecular subtypes of CRC by wide transcriptional genome analysis. CMS1 has microsatellite instability and mutations in CIMP and BRAF pathways. CMS2, distinguished by mutations in specific pathways linked to cellular metabolism, also has a better prognosis. CMS3 has a KRAS mutation as a hallmark. CMS4 presents mutations in fibrogenesis pathways and mesenchymal-epithelial transition, associated with a worse prognosis. CMS classification can be a meaningful step in providing possible answers to important issues in CRC, such as the use of adjuvant chemotherapy in stage II, personalized first-line chemotherapy for metastasic CRC, and possible new target treatments that address specific pathways in each molecular subtype. Understanding CMS is a crucial step in personalized medicine, although prospective clinical trials selecting patients by CMS are required to pass proof-of-concept before becoming a routine clinical tool in oncology routine care.

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Section: Cms and Prognosiscontrasting

confidence: 63%

Consensus molecular subtypes of colorectal cancer in clinical practice: A translational approach

Valenzuela¹,

Canepa²,

Simonetti³

et al. 2021

WJCO

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“…As mentioned above, earlier efforts to implement a CMS classification in a clinical setting have failed, probably due to the robust methodology needed and the lack of prognostic or predictive capabilities, especially with CMS2 and CMS3, which at times comprise more than 50% of the population [ 87 ]. Additionally, in early-stage CC, the number of mesenchymal subtypes (CMS4) is very low, and they sometimes comprise groups with too few events to enable a meaningful statistical analysis [ 18 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Biomarker Panel for Early-Stage Colon Carcinoma

Azcue

Setas

Encı́o

et al. 2021

Cancers

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Molecular characterization of colorectal cancer has helped us understand better the biology of the disease. However, previous efforts have yet to provide significant clinical value in order to be integrated into clinical practice for patients with early-stage colon cancer (CC). The purpose of this study was to assess PD-L1, GLUT-1, e-cadherin, MUC2, CDX2, and microsatellite instability (dMMR) and to propose a risk-panel with prognostic capabilities. Biomarkers were immunohistochemically assessed through tissue microarrays in a cohort of 144 patients with stage II/III colon cancer. A biomarker panel consisting of PD-L1, GLUT-1, dMMR, and potentially CDX2 was constructed that divided patients into low, medium, and high risk of overall survival or disease-free survival (DFS) in equally sized groups. Compared with low-risk patients, medium-risk patients have almost twice the risk of death (HR = 2.10 (0.99–4.46), p = 0.054), while high-risk patients have almost four times the risk (HR = 3.79 (1.77–8.11), p = 0.001). The multivariate goodness of fit was 0.756 and was correlated with Kaplan–Meier curves (p = 0.002). Consistent results were found for DFS. This study provides a critical basis for the future development of an immunohistochemical assessment capable of discerning early-stage CC patients as a function of their prognosis. This tool may aid with treatment personalization in daily clinical practice and improve survival outcomes.

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“…CMS is a stratification system based on the biological characteristics of CRC patients that has recently emerged [ 47 ]. Recently, Purcell et al suggested that consensus molecular subtyping is used, as it improves the prognosis of TNM II stage CRC patients [ 48 ]. Our results show that TNM II stage patients can be sub-grouped into two distinct strata, with different survival probability: patients with lower circ-BCL2L12-1 levels show longer OS intervals, close enough to those of TNM I stage patients, while patients with higher circ-BCL2L12-1 levels show shorter OS intervals, even shorter than those of TNM III stage patients ( Figure 4 b).…”

Section: Discussionmentioning

confidence: 99%

Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer

Karousi

Artemaki

Sotiropoulou

et al. 2020

IJMS

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The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from BCL2L12, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two BCL2L12 circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel BCL2L12 circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.

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Molecular subtyping improves prognostication of Stage 2 colorectal cancer

Cited by 16 publications

References 35 publications

Consensus molecular subtypes of colorectal cancer in clinical practice: A translational approach

Consensus molecular subtypes of colorectal cancer in clinical practice: A translational approach

A Novel Prognostic Biomarker Panel for Early-Stage Colon Carcinoma

Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer

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