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, SP, Brazil.
Laboratory of Extracellular Matrix and Gene Regulation, Department of Structural and Functional Biology, Institute of Biology (IB), University of Campinas (UNICAMP), Campinas 13083-862, SP, Brazil.
Int J Mol Sci. 2022 Aug 17;23(16):9224. doi: 10.3390/ijms23169224.
Prostate cancer (PCa) is the second most common cause of mortality among men. Tumor secretome is a promising strategy for understanding the biology of tumor cells and providing markers for disease progression and patient outcomes. Here, transcriptomic-based secretome analysis was performed on the PCa tumor transcriptome of Genetically Engineered Mouse Model (GEMM) mice to identify potentially secreted and membrane proteins-PSPs and PMPs. We combined a selection of transcripts from the GSE 94574 dataset and a list of protein-coding genes of the secretome and membrane proteome datasets using the Human Protein Atlas Secretome. Notably, nine deregulated PMPs and PSPs were identified in PCa (, , , , , , , , and ). We verified the gene expression patterns of Differentially Expressed Genes (DEGs) in normal and tumoral human samples using the GEPIA tool. , , and targets were downregulated in PCa samples and in the GSE dataset. A significant association between shorter survival and , , , and expression was detected in the MSKCC dataset. We further identified six validated miRNAs (mmu-miR-6962-3p, mmu-miR- 6989-3p, mmu-miR-6998-3p, mmu-miR-5627-5p, mmu-miR-15a-3p, and mmu-miR-6922-3p) interactions that target , , , and . We have characterized the PCa secretome and membrane proteome and have spotted new dysregulated target candidates in PCa.
前列腺癌（PCa）是男性死亡的第二大主要原因。肿瘤分泌组是了解肿瘤细胞生物学并提供疾病进展和患者预后标志物的有前途的策略。在这里，对 Genetically Engineered Mouse Model (GEMM) 小鼠的 PCa 肿瘤转录组进行了基于转录组的分泌组分析，以鉴定潜在的分泌蛋白和膜蛋白-PSPs 和 PMPs。我们结合了 GSE94574 数据集的一部分转录本和 Human Protein Atlas Secretome 中的分泌组和膜蛋白组数据集的蛋白质编码基因列表。值得注意的是，在 PCa 中鉴定出了 9 种失调的 PMPs 和 PSPs（，，，，，，，和）。我们使用 GEPIA 工具验证了正常和肿瘤人类样本中差异表达基因（DEGs）的基因表达模式。在 PCa 样本和 GSE 数据集中，，和 靶点下调。在 MSKCC 数据集中检测到较短的生存时间与，，，和 表达之间存在显著关联。我们进一步鉴定了六个经过验证的 miRNAs（mmu-miR-6962-3p、mmu-miR-6989-3p、mmu-miR-6998-3p、mmu-miR-5627-5p、mmu-miR-15a-3p 和 mmu-miR-6922-3p）与，，，和 的靶向作用。我们已经描述了 PCa 的分泌组和膜蛋白组，并在 PCa 中发现了新的失调靶候选物。
