Åberg Anna-Maja, Bergström Sofia Halin, Thysell Elin, Tjon-Kon-Fat Lee-Ann, Nilsson Jonas A, Widmark Anders, Thellenberg-Karlsson Camilla, Bergh Anders, Wikström Pernilla, Lundholm Marie
Department of Medical Biosciences, Pathology, Umeå University, 901 85 Umeå, Sweden.
Department of Radiation Sciences, Oncology, Umeå University, 901 85 Umeå, Sweden.
Cancers (Basel). 2021 May 17;13(10):2424. doi: 10.3390/cancers13102424.
Increasing evidence indicates calcium-binding S100 protein involvement in inflammation and tumor progression. In this prospective study, we evaluated the mRNA levels of two members of this family, and , in peripheral blood mononuclear cells (PBMCs) in a cohort of 121 prostate cancer patients using RT-PCR. Furthermore, monocyte count was determined by flow cytometry. By stratifying patients into different risk groups, according to TNM stage, Gleason score and PSA concentration at diagnosis, expression of and was found to be significantly higher in patients with metastases compared to patients without clinically detectable metastases. In line with this, we observed that the protein levels of S100A9 and S100A12 in plasma were higher in patients with advanced disease. Importantly, in patients with metastases at diagnosis, high monocyte count and high levels of and were significantly associated with short progression free survival (PFS) after androgen deprivation therapy (ADT). High monocyte count and levels were also associated with short cancer-specific survival, with monocyte count providing independent prognostic information. These findings indicate that circulating levels of monocytes, as well as and , could be biomarkers for metastatic prostate cancer associated with particularly poor prognosis.
越来越多的证据表明，钙结合S100蛋白参与炎症和肿瘤进展。在这项前瞻性研究中，我们使用逆转录聚合酶链反应（RT-PCR）评估了121名前列腺癌患者队列外周血单个核细胞（PBMC）中该家族两个成员S100A9和S100A12的mRNA水平。此外，通过流式细胞术测定单核细胞计数。根据诊断时的TNM分期、 Gleason评分和前列腺特异性抗原（PSA）浓度将患者分层为不同风险组，发现与无临床可检测转移的患者相比，有转移的患者中S100A9和S100A12的表达显著更高。与此一致的是，我们观察到晚期疾病患者血浆中S100A9和S100A12的蛋白水平更高。重要的是，在诊断时有转移的患者中，高单核细胞计数以及S100A9和S100A12的高水平与雄激素剥夺治疗（ADT）后短无进展生存期（PFS）显著相关。高单核细胞计数和S100A9水平也与短癌症特异性生存期相关，单核细胞计数提供独立的预后信息。这些发现表明，循环单核细胞水平以及S100A9和S100A12水平可能是与特别差的预后相关的转移性前列腺癌的生物标志物。
