Exosomal ZFPL1 Identifies Neuroendocrine and Stem Cell-Like Prostate Cancer Subtypes?

IF 2.5 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Prostate Pub Date : 2026-06-01 Epub Date: 2026-03-15 DOI:10.1002/pros.70148
Neshat Masud, Johnmesha Sanders, Kenneth A Iczkowski, Girish V Shah
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引用次数: 0

Abstract

Background: Calcitonin (CT) and its receptor promote prostate cancer (PC) progression and metastasis. Identifying downstream CT-regulated genes may provide clinically useful biomarkers.

Methods: Subtraction hybridization was used to identify CT-inducible genes. Expression of zinc finger protein-like 1 (ZFPL1) was examined in malignant versus benign prostate tissues and evaluated for regulation by CT and androgens. Exosomal secretion of ZFPL1 protein was assessed, and plasma levels were measured in PC patients compared with cancer-free individuals. Immunohistochemistry was performed to assess ZFPL1 localization with neuroendocrine (NE) and stem cell markers.

Results: ZFPL1 was strongly expressed in malignant prostates but nearly absent in benign tissues. Its expression was upregulated by both CT and androgens. ZFPL1 protein was secreted through exosomes, and plasma concentrations in PC patients were at least fourfold higher than in cancer-free controls. Immunohistochemistry confirmed ZFPL1 co-localization with NE and stem cell markers, suggesting an association with aggressive, androgen-resistant PC.

Conclusions: ZFPL1 is a CT- and androgen-regulated protein selectively expressed in malignant prostate cells and secreted via exosomes. Its elevated plasma levels and association with aggressive disease highlight its promise as a non-invasive biomarker for PC detection and monitoring.

外泌体ZFPL1识别神经内分泌和干细胞样前列腺癌亚型?
背景:降钙素(CT)及其受体促进前列腺癌(PC)的进展和转移。鉴定下游的ct调控基因可能提供临床有用的生物标志物。方法:采用减法杂交技术鉴定ct诱导基因。我们检测了锌指蛋白样1 (ZFPL1)在恶性和良性前列腺组织中的表达,并通过CT和雄激素评估其调控作用。评估了PC患者外泌体中ZFPL1蛋白的分泌,并测量了PC患者与无癌患者的血浆水平。用神经内分泌(NE)和干细胞标记物进行免疫组化评估ZFPL1的定位。结果:ZFPL1在恶性前列腺组织中表达强烈,而在良性组织中几乎不表达。CT和雄激素均上调其表达。ZFPL1蛋白通过外泌体分泌,PC患者的血浆浓度至少是无癌对照的四倍。免疫组织化学证实ZFPL1与NE和干细胞标记共定位,提示与侵袭性雄激素抗性PC有关。结论:ZFPL1是一种受CT和雄激素调控的蛋白,在恶性前列腺细胞中选择性表达,并通过外泌体分泌。其升高的血浆水平和与侵袭性疾病的关联突出了其作为PC检测和监测的非侵入性生物标志物的前景。
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来源期刊
Prostate
Prostate 医学-泌尿学与肾脏学
CiteScore
5.10
自引率
3.60%
发文量
180
审稿时长
1.5 months
期刊介绍: The Prostate is a peer-reviewed journal dedicated to original studies of this organ and the male accessory glands. It serves as an international medium for these studies, presenting comprehensive coverage of clinical, anatomic, embryologic, physiologic, endocrinologic, and biochemical studies.
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