scholarly journals Identification of Clinically Relevant Molecular Subtypes in Colorectal Cancer: The Dawning of a New Era

2014 ◽  
Vol 19 (5) ◽  
pp. 568-573 ◽  
Author(s):  
Patrick G. Johnston
2021 ◽  
Vol 22 (1) ◽  
pp. 72-86
Author(s):  
M.Yu. Fedyanin ◽  
E.O. Ignatova ◽  
А.А. Tryakin

Attempts to classify tumors in order to substantiate the different course of the disease and response to therapy have undergone significant changes over the past decades and have advanced from the creation of prognostic systems based on the clinical and morphological picture to the division into molecular-genetic subtypes. The latter, based on various omics data, should have opened a new era in oncology, dividing tumors not only according to the prognostic course, but also allowing individualized treatment. However, data from clinical trials, at least in colorectal cancer, show conflicting results. This review is devoted to the critical analysis of the applicability of molecular genetic subtyping of colon tumors in clinical practice.


2020 ◽  
Vol 04 (03) ◽  
pp. 291-302
Author(s):  
Mariam F. Eskander ◽  
Christopher T. Aquina ◽  
Aslam Ejaz ◽  
Timothy M. Pawlik

AbstractAdvances in the field of surgical oncology have turned metastatic colorectal cancer of the liver from a lethal disease to a chronic disease and have ushered in a new era of multimodal therapy for this challenging illness. A better understanding of tumor behavior and more effective systemic therapy have led to the increased use of neoadjuvant therapy. Surgical resection remains the gold standard for treatment but without the size, distribution, and margin restrictions of the past. Lesions are considered resectable if they can safely be removed with tumor-free margins and a sufficient liver remnant. Minimally invasive liver resections are a safe alternative to open surgery and may offer some advantages. Techniques such as portal vein embolization, association of liver partition with portal vein ligation for staged hepatectomy, and radioembolization can be used to grow the liver remnant and allow for resection. If resection is not possible, nonresectional ablation therapy, including radiofrequency and microwave ablation, can be performed alone or in conjunction with resection. This article presents the most up-to-date literature on resection and ablation, with a discussion of current controversies and future directions.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Peter W. Eide ◽  
Seyed H. Moosavi ◽  
Ina A. Eilertsen ◽  
Tuva H. Brunsell ◽  
Jonas Langerud ◽  
...  

AbstractGene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.


2021 ◽  
Vol 157 ◽  
pp. 71-80
Author(s):  
Arndt Stahler ◽  
Volker Heinemann ◽  
Veronika Schuster ◽  
Kathrin Heinrich ◽  
Annika Kurreck ◽  
...  

Author(s):  
Sanne ten Hoorn ◽  
Anne Trinh ◽  
Joan de Jong ◽  
Lianne Koens ◽  
Louis Vermeulen

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3545-3545
Author(s):  
Inge van Den Berg ◽  
Marcel Smid ◽  
Robert R.J. Coebergh van den Braak ◽  
Mark A van de Wiel ◽  
Carolien H. M. Van Deurzen ◽  
...  

3545 Background: Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). Currently available assays can identify CMS1 and CMS4 cases well, while a dedicated test to distinguish CMS2 and 3 is lacking. This study aimed to identify a panel of methylation markers to distinguish between CMS2 and 3 in patients with CRC. Methods: Fresh-frozen tumor tissue of 239 patients with stage I-III CRC was included. CMS classification was performed on RNA-seq data using the single-sample-prediction parameter from the “CMSclassifier” package. Methylation profiles were obtained using the Infinium HumanMethylation450 BeadChip. We performed adaptive group-regularised logistic ridge-regression with post-hoc group-weighted elastic net marker selection to build prediction models for classification of CMS2 and CMS3 based on 15, 10 or 5 markers. Data from TCGAwas used for validation. Results: Overall methylation profiles differed between CMS2 and CMS3. Group-regularisation of the probes was done based on their location either relative to a CpG island or relative to a gene present in the CMS classifier resulting in two different prediction models and subsequently different marker panels. For both panels, even when using only 5 markers, sensitivity, specificity, and accuracy were > 90%. Validation showed comparable performances. Conclusions: Our highly sensitive and specific methylation marker panel can be used to distinguish CMS2 and 3. This enables development of a qPCR DNA methylation assay in patients with CRC to provide a specific and non-invasive classification tool.


Sign in / Sign up

Export Citation Format

Share Document