# Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

**Authors:** Iván Salgado, Ernesto Prado Montes de Oca, Isaac Chairez, Luis Figueroa-Yáñez, Alejandro Pereira-Santana, Andrés Rivera Chávez, Jesús Bernardino Velázquez-Fernandez, Teresa Alvarado Parra, Adriana Vallejo

PMC · DOI: 10.3390/biomedicines12020395 · 2024-02-08

## TL;DR

This study uses deep learning to identify genes and pseudogenes that may help predict survival in pancreatic cancer patients and could serve as potential drug targets.

## Contribution

The study introduces RPS28P7 pseudogene as a novel druggable target in pancreatic cancer through deep learning analysis.

## Key findings

- Genes like EWSR1, FLT3, and GPC3 show higher amplification in deceased pancreatic cancer patients.
- RPS28P7 pseudogene mRNA is up-regulated and may act as a ceRNA sponge for miRNA in dead patients.
- Proposed RPS28P7 as a potential drug target modulatable via small molecules or RNA technology.

## Abstract

The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number 
>4
 times in the dead compared with the alive group) were EWSR1, FLT3, GPC3, HIF1A, HLF, and MEN1. The most highly up-regulated genes (>8.5-fold change) in the death group were RPL30, RPL37, RPS28P7, RPS11, Metazoa_SRP, CAPNS1, FN1, H3−3B, LCN2, and OAZ1. None of their corresponding proteins were up or down-regulated in the death group. The mRNA of the RPS28P7 pseudogene could act as ceRNA sponging the miRNA that was originally directed to the parental gene RPS28. We propose RPS28P7 mRNA as the most druggable target that can be modulated with small molecules or the RNA technology approach. These markers could be added as criteria to patient stratification in future PaCa drug trials, but further validation in the target populations is encouraged.

## Linked entities

- **Genes:** RPS28P7 (ribosomal protein S28 pseudogene 7) [NCBI Gene 646195], EWSR1 (EWS RNA binding protein 1) [NCBI Gene 2130], FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322], GPC3 (glypican 3) [NCBI Gene 2719], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091], HLF (HLF transcription factor, PAR bZIP family member) [NCBI Gene 3131], MEN1 (menin 1) [NCBI Gene 4221], RPL30 (ribosomal protein L30) [NCBI Gene 6156], RPL37 (ribosomal protein L37) [NCBI Gene 6167], RPS11 (ribosomal protein S11) [NCBI Gene 6205], ATG10 (autophagy related 10) [NCBI Gene 427322], CAPNS1 (calpain small subunit 1) [NCBI Gene 826], FN1 (fibronectin 1) [NCBI Gene 2335], H3-3B (H3.3 histone B) [NCBI Gene 3021], LCN2 (lipocalin 2) [NCBI Gene 3934], OAZ1 (ornithine decarboxylase antizyme 1) [NCBI Gene 4946], RPS28 (ribosomal protein S28) [NCBI Gene 6234]
- **Diseases:** pancreatic cancer (MONDO:0005192)

## Full-text entities

- **Genes:** HLF (HLF transcription factor, PAR bZIP family member) [NCBI Gene 3131], CAPNS1 (calpain small subunit 1) [NCBI Gene 826] {aka CALPAIN4, CANP, CANPS, CAPN4, CDPS, CSS1}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, OAZ1 (ornithine decarboxylase antizyme 1) [NCBI Gene 4946] {aka AZ1, AZI, OAZ}, RPL30 (ribosomal protein L30) [NCBI Gene 6156] {aka L30, eL30}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, GPC3 (glypican 3) [NCBI Gene 2719] {aka DGSX, GTR2-2, MXR7, OCI-5, SDYS, SGB}, RPL37 (ribosomal protein L37) [NCBI Gene 6167] {aka L37, eL37}, RPS11 (ribosomal protein S11) [NCBI Gene 6205] {aka S11, uS17}, RPS28P7 (ribosomal protein S28 pseudogene 7) [NCBI Gene 646195] {aka RPS28_3_1160}, EWSR1 (EWS RNA binding protein 1) [NCBI Gene 2130] {aka EWS, EWS-FLI1}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, RPS28 (ribosomal protein S28) [NCBI Gene 6234] {aka DBA15, S28, eS28}, MEN1 (menin 1) [NCBI Gene 4221] {aka MEAI, SCG2}
- **Diseases:** PaCa (MESH:D010190), death (MESH:D003643), early (MESH:C580055)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** H3-3B — Mus musculus (Mouse), Hybridoma (CVCL_N311)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11154313/full.md

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Source: https://tomesphere.com/paper/PMC11154313