Roumeliotou Argyro, Alkahtani Saad, Alarifi Saud, Alkahtane Abdullah A, Stournaras Christos, Kallergi Galatea
Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, Patras, Greece.
Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Front Cell Dev Biol. 2024 Jun 5;12:1399092. doi: 10.3389/fcell.2024.1399092. eCollection 2024.
Previous publications have shown that STIM1, ORAI1, and KDM2B, are implicated in Ca signaling and are highly expressed in various cancer subtypes including prostate cancer. They play multiple roles in cancer cell migration, invasion, and metastasis. In the current study we investigated the expression of the above biomarkers in circulating tumor cells from patients with metastatic prostate cancer. Thirty-two patients were enrolled in this study and CTCs' isolation was performed with Ficoll density gradient. Two different triple immunofluorescence stainings were conducted with the following combination of antibodies: CK/KDM2B/CD45 and CK/STIM1/ORAI1. Slides were analyzed using VyCAP microscopy technology. CTC-positive patients were detected in 41% for (CK/KDM2B/CD45) staining and in 56% for (CK/STIM1/ORAI1) staining. The (CK+/KDM2B+/CD45-) and the (CK+/STIM1+/ORAI1+) were the most frequent phenotypes as they were detected in 85% and 94% of the CTC-positive patients, respectively. Furthermore, the expression of ORAI1 and STIM1 in patients' PBMCs was very low exhibiting them as interesting specific biomarkers for CTC detection. The (CK+/STIM1+/ORAI1+) phenotype was correlated to bone metastasis (, while the (CK+/STIM1+/ORAI1-) to disease relapse (. STIM1, ORAI1, and KDM2B were overexpressed in CTCs from patients with metastatic prostate cancer. STIM1 and ORAI1 expression was related to disease recurrence and bone metastasis. Further investigation of these biomarkers in a larger cohort of patients will clarify their clinical significance for prostate cancer patients.
先前的研究表明，基质相互作用分子1（STIM1）、钙释放激活钙通道蛋白1（ORAI1）和赖氨酸特异性去甲基化酶2B（KDM2B）与钙信号传导有关，并且在包括前列腺癌在内的各种癌症亚型中高表达。它们在癌细胞迁移、侵袭和转移中发挥多种作用。在本研究中，我们调查了上述生物标志物在转移性前列腺癌患者循环肿瘤细胞中的表达。本研究纳入了32名患者，并使用Ficoll密度梯度法进行循环肿瘤细胞（CTC）的分离。使用以下抗体组合进行了两种不同的三重免疫荧光染色：细胞角蛋白（CK）/KDM2B/白细胞共同抗原（CD45）和CK/STIM1/ORAI1。使用VyCAP显微镜技术对玻片进行分析。对于（CK/KDM2B/CD45）染色，41%的患者检测到CTC阳性；对于（CK/STIM1/ORAI1）染色，56%的患者检测到CTC阳性。（CK+/KDM2B+/CD45-）和（CK+/STIM1+/ORAI1+）是最常见的表型，分别在85%和94%的CTC阳性患者中检测到。此外，患者外周血单个核细胞（PBMC）中ORAI1和STIM1的表达非常低，表明它们是用于CTC检测的有趣的特异性生物标志物。（CK+/STIM1+/ORAI1+）表型与骨转移相关（，而（CK+/STIM1+/ORAI1-）与疾病复发相关（。STIM1、ORAI1和KDM2B在转移性前列腺癌患者的CTC中过表达。STIM1和ORAI1的表达与疾病复发和骨转移有关。在更大的患者队列中对这些生物标志物进行进一步研究将阐明它们对前列腺癌患者的临床意义。
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