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Identification of alternative membrane protein isoforms as potential biomarkers for tumors with poor prognosis and scarce therapeutic options

Grant number: 20/14158-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2021
Effective date (End): May 31, 2024
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Pedro Alexandre Favoretto Galante
Grantee:Filipe Ferreira dos Santos
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Splicing is an essential step of gene expression in eukaryotes. Many loci of the human genome, after being transcribed, are processed in an alternative way (alternative splicing), generating different isoforms of mRNAs for the same gene (locus). It is known that changes in the splicing pattern are related to the development of approximately 15% of genetic diseases and, of course, to several types of malignant tumors in humans. Cancer cells, in general, have a high rate of alternative splicing, including tumor-specific isoforms. In this project, we will seek for alternative splicing events in genes encoding cell membrane proteins that occur specifically or preferentially in tumor samples. To do so, we will use gene expression data from a set of ~11,000 samples of 33 Cancer types and a wide repertoire of computational tools (bioinformatics) to process, integrate and analyze this data. As we will select only isoforms that are either specific or preferentially found in tumors from events in genes encoding cell membrane proteins, we expect, at the end of this project, to have a promising set of biomarkers for the deliberate development of new targeted therapies for tumor treatment. In our analyses, we will pay special attention to Cancer types whose treatment options remain scarce, such as Diffuse Intrinsic Pontine Glioma, Glioblastoma, and Pancreatic Adenocarcinoma, for which we already have promising preliminary results. All results generated here will be organized in a database with free access and disseminated to the scientific community. In conclusion, we hope that our findings will help in the development of new targeted therapies for Cancer, especially for those tumors with a high mortality rate and that do not yet have good target drugs or highly effective treatments. (AU)

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