scholarly journals ROLE OF PD-L1 ASSESSMENT IN THE ASPECT OF MOLECULAR-GENETIC CLASSIFICATION OF COLORECTAL CANCER. CURRENT STATE OF THE PROBLEM

2021 ◽  
Vol 20 (1) ◽  
pp. 115-122
Author(s):  
S. V. Vtorushin ◽  
S. S. Naumov ◽  
I. V. Stepanov ◽  
L. E. Sinyansky ◽  
S. G. Afanasyev
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Molecular Subtypes ◽  
Malignant Tumors ◽  
Molecular Genetic ◽  
Cochrane Library ◽  
Colorectal Carcinomas ◽  
Genetic Classification ◽  
Current State

The purpose of the study was to analyze and summarize data regarding a significance of PD -L1 expression in various molecular subtypes of colorectal cancer.Material and Methods. A systemic literature search was conducted in the electronic databases Medline, Cochrane Library, Elibrary, PubMed. Of identified and reviewed 201 full-text articles, we included data from 47 studies.Results. The literature review described the features of the molecular genetic classification of colorectal cancer and revealed the key characteristics of each of the molecular subtypes of this disease. Much attention was paid to the molecular mechanisms of anti-PD -1/PD -L1 therapy. The main problems associated with the standardization of methods for pathomorphological assessment of the expression of this marker and the difficulties of its interpretation in colorectal carcinomas were outlined.Conclusion. Analysis of the literature revealed problems associated with the assessment of PD -L1 expression in colorectal cancer, in particular, with the lack of generally accepted methods for interpreting research results and standardizing methods for pathomorphological diagnosis of malignant tumors of this localization. Further studies are needed for introducing the molecular genetic classification of colorectal carcinomas into a wide clinical practice and personalizing the approach to therapy of this disease.

Abstract 2276: Genetic classification of colorectal cancer

2021 ◽  
Author(s):  
Yoshikage Inoue ◽  
Nobuyuki Kakiuchi ◽  
Kenichi Yoshida ◽  
Yasuhito Nanya ◽  
Yusuke Shiozawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Classification

Classification of Colorectal Cancer in Molecular Subtypes by Immunohistochemistry

2018 ◽  
pp. 179-191 ◽  
Author(s):  
Sanne ten Hoorn ◽  
Anne Trinh ◽  
Joan de Jong ◽  
Lianne Koens ◽  
Louis Vermeulen
Keyword(s):  
Colorectal Cancer ◽  
Molecular Subtypes

A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer.

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 ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Prediction Models ◽  
Molecular Subtypes ◽  
Cpg Island ◽  
Methylation Marker ◽  
Marker Selection ◽  
Fresh Frozen ◽  
Classification Tool

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.

Clinical importance of molecular markers of adult diffuse glioma

2019 ◽  
Vol 19 (5) ◽  
pp. 412-416 ◽  
Author(s):  
Emanuela Molinari ◽  
Olimpia E Curran ◽  
Robin Grant
Keyword(s):  
Molecular Markers ◽  
Molecular Genetic ◽  
Clinical Importance ◽  
Response To Treatment ◽  
Low Grade ◽  
Diffuse Glioma ◽  
Wild Type ◽  
Genetic Classification ◽  
Cns Tumours

In 2016, the WHO incorporated molecular markers, in addition to histology, into the diagnostic classification of central nervous system (CNS) tumours. This improves diagnostic accuracy and prognostication: oligo-astrocytoma no longer exists as a clinical entity; isocitrate dehydrogenase (IDH) mutant and 1p/19q co-deleted oligodendroglioma is a smaller category with better prognosis; IDH wild-type ‘low-grade’ glioma has a much poorer prognosis; and glioblastoma is divided into IDH mutant (with an better prognosis than pre-2016 glioblastoma) and IDH wild type (with a poorer prognosis). Previous advice based on phenotype alone will change with respect to median survival, best management plan and response to treatment. There are implications for routine neuropathology reporting and future trial design. Cases that are difficult to classify may need more advanced molecular genetic classification through DNA methylation-based classification of CNS tumours (Heidelberg Classifier). We discuss the practical implications.

scholarly journals Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer

Oncotarget ◽  
2018 ◽  
Vol 9 (27) ◽  
pp. 18698-18711 ◽  
Author(s):  
Akira Okita ◽  
Shin Takahashi ◽  
Kota Ouchi ◽  
Masahiro Inoue ◽  
Mika Watanabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Predictive Factor ◽  
Molecular Subtypes ◽  
Chemotherapeutic Efficacy

Toward a Molecular-Genetic Classification of Spitzoid Neoplasms

2017 ◽  
Vol 37 (3) ◽  
pp. 431-448 ◽  
Author(s):  
Michael T. Tetzlaff ◽  
Alexandre Reuben ◽  
Steven D. Billings ◽  
Victor G. Prieto ◽  
Jonathan L. Curry
Keyword(s):  
Molecular Genetic ◽  
Genetic Classification

MicroRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key mircRNAs

2020 ◽  
Author(s):  
Liang Wang ◽  
Jun Yang ◽  
Jian Huang ◽  
Zheng-Qi Wen ◽  
Ning Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Expression Level ◽  
Cancer Tissue ◽  
Potential Biomarker

Abstract Objective: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC.Methods: The infiltration and metastasis of neutrophils in Primary colorectal cancer tissue and Paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-β1 in vitro, exosomes were extracted and sequenced, and then the expression differences of microRNAs were screened by using Agilent microRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using Targetscan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed microRNA using quantitative Realtime polymerase chain reaction (RT-PCR) was validated.Results: A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 were validated in accordance with the results of RT-PCR.Conclusion: The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells, and provided the potential biomarker for prognosis for clinical treatment of CRC

scholarly journals ID:2037 Molecular mechanisms underlying resistance to MEK1/2 inhibitor in BRAF-mutated colorectal cancer

2017 ◽  
Vol 4 (S) ◽  
pp. 68
Author(s):  
Hong-Quan Duong
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Scaffold Protein ◽  
Colorectal Carcinomas ◽  
Intrinsic Resistance ◽  
Oncogenic Signaling ◽  
Colorectal Cancer Cells

Colorectal carcinomas are characterized by multiple genetic alterations, including constitutive Wnt activity and gain-of-function mutations in K-RAS and B-RAF. BRAF encodes a Ser/Thr kinase acting in the Ras/MEK/ERK pathway and the V600E mutation found in 11% of colorectal cancers renders this kinase constitutively active. B-RAF mutated colorectal carcinomas represents a very aggressive entity with a poor prognosis. Understanding the molecular mechanisms activated downstream of mutated B-RAF is urgently needed to design new therapeutic avenues to treat B-ARF mutated colorectal carcinomas and to circumvent resistance to therapies targeting the Ras/Raf/MEK1/ERK1/2 pathway. In a search for candidates that critically contribute to both intrinsic and acquired resistance to MEK1 inhibition in B-RAF mutated colorectal cancer cells, we identified one scaffold protein whose expression is driven by both NF-kB and AP-1 families of transcription factors. This scaffold protein promotes the expression of HER2 and HER3 in colorectal cancer cells subjected to MEK1 or B-RAF inhibition (Selumetinib and Vemurafenib, respectively) and, as such, is critically involved in the intrinsic resistance to these targeted therapies. The same scaffold protein is also strongly induced in B-RAF but not K-RAS mutated colorectal cancer cells showing acquired resistance to MEK1 inhibition. Interfering with the expression of this scaffold protein circumvents both intrinsic and acquired resistance to Selumetinib in B-RAF mutated colorectal cancer cells. Our study defines a new molecular actor critically involved in oncogenic signaling pathways triggered by mutated B-RAF. Our study also defineS new combinatory therapies to better treat B-RAF-mutated colorectal carcinomas.

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