背景:最近,研究表明,外泌体生物标志物和DNA错配修复蛋白(MMR)可在癌症风险分层和预后评估中发挥重要作用.前列腺癌(PCa)诊断的金标准是活检和组织病理学检查。因此,外泌体和MMR蛋白的复杂评估可能有助于前列腺癌风险分层和诊断.本研究的目的是评估和比较前列腺良性增生(BPH)和PCa患者组织中外泌体蛋白CD9和CD63以及MMR蛋白的表达。
方法:本研究为回顾性研究。总之,92例PCa患者和20例BPH患者(对照组)被纳入研究。通过免疫组织化学(IHC)分析外泌体和MMR蛋白表达。我们研究中每位PCa患者的随访持续到疾病进展和/或最多5年。
结果:在56例患者中观察到低级别PCa,在36例患者中观察到高级别PCa。与低级别PCa患者相比,高级别PCa患者的CD63表达明显更高。与对照组相比,PCa患者的CD9表达显着下调。在10例PCa患者中观察到MMR蛋白表达缺乏。在所有BPH病例中均维持MMR蛋白。研究发现MMR蛋白丢失与PCaISUP分级组之间呈负相关。MMR缺乏患者的无进展生存期(PFS)明显短于MMR表达维持的患者。
结论:CD9蛋白表达在PCa中下调,与BPH相比,而CD63蛋白表达在高级别PCa中上调,而在低级别PCa中下调。CD63蛋白上调,CD9下调,MMR蛋白的丢失是高级别PCa患者PFS较短的特征。CD9、CD63和MMR可能是PCa诊断和危险分层的常规免疫组织化学生物标志物。
BACKGROUND: Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa.
METHODS: The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years.
RESULTS: Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression.
CONCLUSIONS: CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.