Designing of functional magnetic semiconductor materials for spintronic devices
2025-05-15 12:04
The aim of the project: The aim of the project: Studying the genomic profile of patients with colorectal cancer to predict clinical outcomes based on molecular markers
Project Description: Discoveries in the field of research into the mechanisms of oncogenesis over the past three decades have led to advances in diagnostics and a decrease in mortality among patients with colorectal cancer (CRC). However, survival prognoses among patients with CRC remain inaccurate. Most standard CRC treatments have little effect, and the five-year relapse rate exceeds 90% of cases. Heterogeneous response to therapeutic treatment of CRC and survival prognoses are largely due to various genotypic and phenotypic features of the tumor. Clinical, morphological and molecular - genetic characteristics of the tumor are increasingly recognized as important criteria for assessing the response to therapy and predicting the course of the disease. Therefore, the search for molecular markers that allow rapid assessment of the effectiveness of selected therapy and relapse prognosis is an urgent task of clinical practice in a personalized approach to cancer therapy. With the development of sequencing technologies, it has become possible to quickly assess a wide range of mutations in the entire genomic profile of a patient. Comprehensive genomic profiling (CGP) is an effective precision medicine application that takes advantage of next-generation sequencing (NGS) to assess a wide range of biomarkers in a single assay. Despite ongoing studies on the genetics of CRC, there have been no previous studies of the full genomic profile of CRC patients to comprehensively assess all known molecular markers, including MSI and TMB, in a single test to select individual therapy in Kazakhstan. Therefore, this study is relevant for Kazakhstan
Expected results: The results obtained during the implementation of the project will be published in at least 2 (two) articles and (or) reviews in peer-reviewed scientific publications in the scientific direction of the project, indexed in the Science Citation Index Expanded database of the Web of Science and (or) having a percentile according to CiteScore in the database Scopus at least 50 (fifty), and in at least 1 (one) article or review in a peer-reviewed foreign or domestic publication recommended by CQAFSHE. As a result of the project, the most significant genetic markers will be identified. A comprehensive assessment of the influence of clinical, histological characteristics of tumors and molecular markers on the possibility of progression and relapses with personalized therapy will be carried out. The data obtained during the implementation of the project will be of a recommendatory nature in practical medicine when selecting personalized treatment, as well as when monitoring the effectiveness of drug therapy in patients with CRC
Methodology: Recruitment of biomaterial (surgical, biopsy material, and paraffinized tissue samples fixed in formalin) from patients with stage II-IV colorectal cancer. Preparation, staining, and pathomorphological analysis of histological glass slides of tumor material sections from paraffin blocks. Immunohistochemical analysis of histological slides for key molecular markers. DNA extraction from tumor tissue sections confirmed morphologically with more than 50% altered tumor cells. Quantitative and qualitative assessment of DNA by spectrophotometric and fluorimetric methods. Preparation of libraries and sequencing of samples by next-generation sequencing (NGS). Bioinformatics analysis of sequencing data. Evaluation of the prognostic significance of molecular markers of single nucleotide variants (SNV), microsatellite instability (MSI), and tumor burden (TMB) in patients with CRC in personalized therapy