Lygirou Vasiliki, Fasoulakis Konstantinos, Stroggilos Rafael, Makridakis Manousos, Latosinska Agnieszka, Frantzi Maria, Katafigiotis Ioannis, Alamanis Christos, Stravodimos Konstantinos G, Constantinides Constantinos A, Vlahou Antonia, Zoidakis Jerome
Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece.
Department of Urology, Ippokrateio General Hospital of Athens, 114 Vasilissis Sofias Avenue, 11527 Athens, Greece.
Cancers (Basel). 2022 Aug 2;14(15):3765. doi: 10.3390/cancers14153765.
Prostate cancer (PCa) is the second most common cancer in men. Diagnosis and risk assessment are widely based on serum Prostate Specific Antigen (PSA) and biopsy, which might not represent the exact degree of PCa risk. Towards the discovery of biomarkers for better patient stratification, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Comparative analysis of 86 PCa samples among grade groups 1-5 identified 301 significantly altered proteins. Additional analysis based on biochemical recurrence (BCR; BCR+ = 14, BCR- = 51) revealed 197 significantly altered proteins that indicate disease persistence. Filtering the overlapping proteins of these analyses, seven proteins (, , , , , , ) had increased expression in advanced grades and in BCR+/BCR- and may play a critical role in PCa aggressiveness. Notably, all seven proteins were significantly associated with progression in Prostate Cancer Transcriptome Atles (PCTA) and , , and were further validated in The Cancer Genome Atlas (TCGA), where they were upregulated in BCR+/BCR-. levels were also associated with poorer 5-year survival. Our study provides valuable insights into the key regulators of PCa progression and aggressiveness. The seven selected proteins could be used for the development of risk assessment tools.
前列腺癌（PCa）是男性中第二常见的癌症。诊断和风险评估广泛基于血清前列腺特异性抗原（PSA）和活检，而这可能无法准确反映PCa的风险程度。为了发现用于更好地对患者进行分层的生物标志物，我们使用液相色谱与串联质谱联用（LC-MS/MS）对福尔马林固定石蜡包埋（FFPE）前列腺组织标本进行了蛋白质组学分析。对1-5级组中的86个PCa样本进行比较分析，鉴定出301种显著改变的蛋白质。基于生化复发（BCR；BCR+ = 14，BCR- = 51）的进一步分析揭示了197种显著改变的蛋白质，这些蛋白质表明疾病持续存在。对这些分析中的重叠蛋白质进行筛选，七种蛋白质（，，，，，，）在高级别以及BCR+/BCR-中表达增加，可能在PCa侵袭性中起关键作用。值得注意的是，所有七种蛋白质在前列腺癌转录组图谱（PCTA）中均与进展显著相关，并且，，和在癌症基因组图谱（TCGA）中得到进一步验证，在那里它们在BCR+/BCR-中上调。水平也与较差的5年生存率相关。我们的研究为PCa进展和侵袭性的关键调节因子提供了有价值的见解。所选的七种蛋白质可用于开发风险评估工具。
