# SLIT/ROBO Pathway and Prostate Cancer: Gene and Protein Expression and Their Prognostic Values

**Authors:** Nilton J. Santos, Francielle C. Mosele, Caroline N. Barquilha, Isabela C. Barbosa, Flávio de Oliveira Lima, Guilherme Oliveira Barbosa, Hernandes F. Carvalho, Flávia Karina Delella, Sérgio Luis Felisbino

PMC · DOI: 10.3390/ijms26115265 · 2025-05-30

## TL;DR

This study explores the SLIT/ROBO pathway in prostate cancer, identifying potential biomarkers and therapeutic targets for better prognosis and treatment.

## Contribution

The study characterizes the SLIT/ROBO pathway's gene and protein expression in prostate cancer using mouse models and human data, revealing novel prognostic markers.

## Key findings

- Transcriptomic analysis showed altered SLIT/ROBO gene expression in prostate tumors.
- SLIT1, SLIT2, ROBO1, and ROBO4 expression correlated with patient prognosis in subgroups.
- The SLIT/ROBO pathway shows potential as a therapeutic target in prostate cancer.

## Abstract

Prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer-related mortality among men. Gene expression analysis has been crucial in understanding tumor biology and providing disease progression markers. Cell surface glycoproteins and those in the extracellular matrix play significant roles in the PCa microenvironment by promoting migration, invasion, and metastasis. The molecular and histopathological heterogeneity of prostate tumors necessitates a new marker discovery to better stratify patients at risk for poor prognosis. In this study, our objectives were to investigate and characterize the localization and expression of SLIT/ROBO in PCa samples from transgenic mice and human tumor samples, aiming to identify novel prognostic markers and potential therapeutic targets. We conducted histopathological, immunohistochemical, and bioinformatics analyses on prostate tumors from two knockout mice models (Pb-Cre4/Ptenf/f and Pb-Cre4/Trp53f/f;Rb1f/f) and human prostate tumors. Transcriptomic analyses revealed special changes in the expression of genes related to the SLIT/ROBO neural signaling pathway. We further characterized the gene and protein expression of the SLIT/ROBO pathway in knockout animal samples, and protein expression in the PCa samples of patients with different Gleason scores. Public datasets with clinical data from patients (The Human Protein Atlas, cBioPortal, SurvExpress and CamcAPP) were used to validate the gene and protein expression of SLIT1, SLIT2, ROBO1, and ROBO4, correlating these alterations with the prognosis of subgroups of patients. Our findings highlight potential biomarkers of the SLIT/ROBO pathway with prognostic and predictive value, as well as promising therapeutic targets for PCa.

## Linked entities

- **Genes:** SLIT1 (slit guidance ligand 1) [NCBI Gene 6585], SLIT2 (slit guidance ligand 2) [NCBI Gene 9353], ROBO1 (roundabout guidance receptor 1) [NCBI Gene 6091], ROBO4 (roundabout guidance receptor 4) [NCBI Gene 54538], PTEN (phosphatase and tensin homolog) [NCBI Gene 5728], TP53 (tumor protein p53) [NCBI Gene 7157], RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925]
- **Diseases:** prostate cancer (MONDO:0005159)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** ROBO4 (roundabout guidance receptor 4) [NCBI Gene 54538] {aka AOVD3, ECSM4, MRB}, SLIT2 (slit guidance ligand 2) [NCBI Gene 9353] {aka SLIL3, Slit-2}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925] {aka OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb}, ROBO1 (roundabout guidance receptor 1) [NCBI Gene 6091] {aka CPHD8, DUTT1, NORS, NYS8, SAX3}, SLIT1 (slit guidance ligand 1) [NCBI Gene 6585] {aka MEGF4, SLIL1, SLIT-1, SLIT3}
- **Diseases:** PCa (MESH:D011471), prostate tumors (MESH:D011472), cancer (MESH:D009369), metastasis (MESH:D009362)
- **Chemicals:** Pb (MESH:D007854)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12155087/full.md

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Source: https://tomesphere.com/paper/PMC12155087