Santos Nilton J, Mosele Francielle C, Barquilha Caroline N, Barbosa Isabela C, Lima Flávio de Oliveira, Barbosa Guilherme Oliveira, Carvalho Hernandes F, Delella Flávia Karina, Felisbino Sérgio Luis
Laboratory of Extracellular Matrix Biology, Department of Structural and Functional Biology, Institute of Biosciences of Botucatu (IBB), São Paulo State University (UNESP), Botucatu 18618-689, São Paulo, Brazil.
Laboratory of Extracellular Matrix and Gene Regulation, Department of Structural and Functional Biology, Institute of Biology (IB), University of Campinas (UNICAMP), Campinas 13083-865, São Paulo, Brazil.
Int J Mol Sci. 2025 May 30;26(11):5265. doi: 10.3390/ijms26115265.
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 mice models ( and ) 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.
前列腺癌（PCa）是男性中第二常见的癌症，也是癌症相关死亡的第二大主要原因。基因表达分析对于理解肿瘤生物学和提供疾病进展标志物至关重要。细胞表面糖蛋白和细胞外基质中的糖蛋白通过促进迁移、侵袭和转移在PCa微环境中发挥重要作用。前列腺肿瘤的分子和组织病理学异质性需要发现新的标志物，以便更好地对预后不良风险的患者进行分层。在本研究中，我们的目标是研究和表征SLIT/ROBO在转基因小鼠和人类肿瘤样本的PCa样本中的定位和表达，旨在识别新的预后标志物和潜在的治疗靶点。我们对两种小鼠模型（和）的前列腺肿瘤以及人类前列腺肿瘤进行了组织病理学、免疫组织化学和生物信息学分析。转录组分析揭示了与SLIT/ROBO神经信号通路相关基因表达的特殊变化。我们进一步表征了基因敲除动物样本中SLIT/ROBO通路的基因和蛋白质表达，以及不同Gleason评分患者的PCa样本中的蛋白质表达。使用来自患者的具有临床数据的公共数据集（人类蛋白质图谱、cBioPortal、SurvExpress和CamcAPP）来验证SLIT1、SLIT2、ROBO1和ROBO4的基因和蛋白质表达，并将这些改变与患者亚组的预后相关联。我们的研究结果突出了SLIT/ROBO通路具有预后和预测价值的潜在生物标志物，以及PCa有前景的治疗靶点。
