Comparative investigation and characterization of transcriptome profiles from patients with esophageal squamous cell carcinoma

Esophageal cancer ranks sixth in prevalence among all types of cancer in Kazakhstan and is characterized by a low level of detection. Due to epidemiological and genetic differences between different populations, the difficulty of choosing treatment for specific groups of patients and histological forms of esophageal cancer increases. Therefore, it is necessary to study and investigate the population-specific cause of the occurrence and development of
esophageal cancer at the genomic, transcriptomic and proteomic levels. A comprehensive study of the molecular mechanisms (gene expression, genomic rearrangements and translocations, regulation using non-coding RNAs, functional study of fusion genes, DNA methylation, single-cell RNA sequencing) of the occurrence and progression of esophageal cancer using "omics" technologies is the key to identifying biomarkers for early diagnosis and targeted therapy. Understanding the pathogenesis of esophageal cancer will allow for more effective approaches to early diagnosis of the disease and further treatment strategies. Currently, the development of biomedicine is closely related to the development of new analysis approaches in post-"omics" research. Significant progress in the field of genomics, transcriptomics, proteomics and bioinformatics allows the use of modern technologies and methods for the comprehensive study and diagnosis of many diseases. Cancer research is one of the most important sources of large-scale molecular profiling data. An urgent task of modern bioinformatics and systems biology is the detailed study of huge arrays of "multi-
omics" data, which requires the use of reliable mathematical and statistical methods to search for and detect hidden signals and signaling pathways that regulate the development and functional activity of cancer cells.

The main goal of the project is to study transcriptomic profiles of Kazakhstani patients with squamous cell esophageal cancer and to study in detail the expression of non-coding RNAs in comparison with esophageal adenocarcinoma. The results of our preliminary studies of cancer transcriptome profiles of Kazakhstani patients revealed differentially expressed genes that require additional experimental work on the validation of detected genes, validation of detected fusion genes, as well as new experimental work on the study of non-coding RNAs (microRNAs, small and long non-coding RNAs) in tumor tissues. It is also planned to conduct a meta-analysis of various transcriptomic datasets of esophageal cancer using Independent Components Analysis for a comparative study of reproducible molecular signals and signaling pathways.

Tasks of the project:
- Extraction and evaluation of the quality of RNA from tumor tissues of Kazakhstani patients with esophageal cancer will be carried out;
- The detection of the expression of individual genes in the tumor tissues of Kazakhstani patients with esophageal cancer using RT-PCR technology will be carried out;
-Previously identified fusion genes in tumor tissues of Kazakhstani patients with esophageal cancer will be evaluated using RT-PCR technology;
- Targeted profiling of non-coding RNAs will be carried out using next-generation sequencing technologies;
- Identification of non-coding RNAs in tumor tissues of Kazakhstani patients with esophageal cancer using bioinformatics methods will be carried out;
- Comparative meta-analysis of transcriptomic profiles using Independent Components Analysis and identification of reproducible molecular signaling pathways characteristic of esophageal cancer will be carried out;