Laboratory of Translational Oncology, Institute of Medical Biotechnology and Experimental Oncology, Medical University of Gdańsk, Gdańsk, Poland.
FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology (IFOM), Milan, Italy.
Br J Cancer. 2020 Dec;123(12):1767-1774. doi: 10.1038/s41416-020-01052-8. Epub 2020 Sep 9.
Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination.
EGFR overexpression (EGFR) was tracked in 1039 primary tumours, circulating tumour cells from 39 d'Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices.
EGFR was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFR correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFR was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness.
EGFR is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones.
前列腺癌（PCa）是男性最常见的恶性肿瘤之一。虽然局部疾病患者的 5 年生存率接近 100%，但转移性疾病仍然无法治愈。因此，需要有表明转移扩散的标志物。
在 1039 例原发性肿瘤、39 例达米科高危患者的循环肿瘤细胞和 21 例去势抵抗性前列腺癌病例的转移样本中跟踪 EGFR 过表达（EGFR）。将 EGFR 状态与临床参数进行比较，并通过免疫组织化学和基因本体分析评估多种分子因素。通过在软质和硬质基质上种植 PC-3 细胞来评估 EGFR 的功能方面。
在 14%的原发性肿瘤中发现了 EGFR，它与无转移生存时间缩短有关，是总体生存较差的独立指标。EGFR 与肿瘤细胞的促迁移和促转移表型以及丰富的胶原纤维含量相关。所有循环肿瘤细胞（在 13%的病例中检测到）均为 EGFR 阳性，与 EMT 相关表型无关。EGFR 在去势抵抗性骨转移中更为普遍（29%的患者），并支持人类前列腺癌细胞在刚性基质上的生长，模拟骨硬度。
EGFR 是一种稳定的、与 EMT 无关的前列腺癌标志物，可扩散至刚性器官，优先扩散至骨骼。
