IDENTIFICATION OF ALTERNATIVE ISOFORMS OF HUMAN CELLULAR MEMBRANE PROTEINS AS POTENTIAL BIOMARKERS FOR TUMORS WITH POOR PROGNOSIS AND FEW THERAPEUTIC OPTIONS

Filipe Ferreira dos Santos; Pedro A F Galante

Paper Title

Authors

Filipe Ferreira dos Santos
Pedro A F Galante

Modality

Poster

Subject area

RNA and transcriptomics

Publishing Date

08/11/2023

Country of Publishing

Brazil | Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeeting2023/634809-identification-of-alternative-isoforms-of-human-cellular-membrane-proteins-as-potential-biomarkers-for-tumors-wit

ISBN

978-65-272-0061-1

Keywords

Cellular Membrane Proteins, Alternative Splicing, Gene Expression, Rectum Adenocarcinoma, Human Surfaceome

Summary

Splicing is an essential step of post-transcriptional processing and gene expression. In humans, approximately 95% of multi-exonic coding genes have at least two alternatively spliced (AS) isoforms, enabling an increase of protein diversity. The growing generation and organization (in databases) of sequencing data, coupled with the creation of advanced methodologies for their analysis, has helped to accelerate our understanding regarding this molecular mechanism. For instance, various tumor-specific isoforms of some genes have been associated with the hallmarks of cancer. However, specific AS patterns for cell membrane proteins (CMP) are still poorly explored, yet have shown potential, especially due to the urgent need of seeking new treatment alternatives for diseased patients. Therefore, this work aims to catalog and characterize all human CMPs to allow the systematic study of the landscape of AS in the “surfaceome”, identifying isoforms specifically or preferentially expressed in different tumor types. Subsequently, clinical and molecular (expression by RNA sequencing) data of 90 samples of rectum adenocarcinoma (READ; 46 located in the rectum and the other 44 in the rectosigmoid junction) were used. We developed, after a number of filters and manual curation, a reliable and consistent CMP catalog (“surfaceome”) containing 16,978 transcripts of 3,563 CMPs. Representative isoforms, which are not always in the membrane, have, in general, a greater number (4 [1-7]) of transmembrane regions (TMRs) when compared to the alternatives (1 [0-4 ] ]). Interestingly, more than half of all isoforms lack either the signal peptide (SP) or GPI anchors, although we found about 60% of the surfaceome in the membrane. The READ dataset helped us to consolidate the pipelines, which will soon be applied to other tissues. We found 54 DETs and 8 DEGs in the rectosigmoid junction relative to the rectum (|L2FC| = 1), but only 4 differential AS events (|?PSI| ? 0). Preliminary analyzes for the TSPAN6 gene indicate that we are likely to find a large number of AS events occurring in relevant regions of CMPs, mostly TMRs. Isoforms originating from these cases are the best candidates for new prognostic biomarkers and promising therapeutic targets.

Title of the Event: X-Meeting / BSB 2023
City of the Event: Curitiba
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

SANTOS, Filipe Ferreira dos; GALANTE, Pedro A F. IDENTIFICATION OF ALTERNATIVE ISOFORMS OF HUMAN CELLULAR MEMBRANE PROTEINS AS POTENTIAL BIOMARKERS FOR TUMORS WITH POOR PROGNOSIS AND FEW THERAPEUTIC OPTIONS.. In: X-Meeting presentations. Anais...Curitiba(PR) Campus da indústria, 2023. Available in: https//www.even3.com.br/anais/xmeeting2023/634809-IDENTIFICATION-OF-ALTERNATIVE-ISOFORMS-OF-HUMAN-CELLULAR-MEMBRANE-PROTEINS-AS-POTENTIAL-BIOMARKERS-FOR-TUMORS-WIT. Access in: 13/06/2025