High expression of ladinin-1 (LAD1) predicts adverse outcomes: a new candidate docetaxel resistance gene for prostatic cancer (PCa)

Docetaxel resistance is one of the major obstacles that undermine the treatment outcome of PCa. Exploring molecular mechanisms associated with docetaxel resistance could provide insights into the formulation of novel strategies enhancing the efficacy of PCa treatment. Ladinin-1 (LAD1) is an anchoring filament protein in basement membranes, which contributes to the association of the epithelial cells with the underlying mesenchyme. LAD1 has been implicated in the progression of different cancers. However, its role in PCa remains to be investigated. In the present study, we found that LAD1 was highly expressed in docetaxel-resistant PCa cells, while its expression was significantly suppressed in tumor samples after docetaxel treatment. Moreover, the expression level of LAD1 in PCa tissues was significantly higher than that of normal tissue, and high expression level of LAD1 was significantly associated with adverse outcomes of PCa patients. Finally, high expression of LAD1 in PCa tissue was also correlated with the expression level of genes involving in tumor cell proliferation and invasive behaviors. Collectively, our data suggest that LAD1 may serve as a potential prognostic factor in PCa patients.

多西他赛（Docetaxel）耐药是影响前列腺癌（Prostate Cancer, PCa）治疗结局的主要障碍之一。探究与多西他赛耐药相关的分子机制，可为制定提升前列腺癌治疗疗效的新型策略提供理论依据。拉迪宁-1（Ladinin-1, LAD1）是基底膜中的锚定丝蛋白，可介导上皮细胞与下方间充质的附着结合。现有研究表明，LAD1与多种癌症的进展密切相关，但其在前列腺癌中的具体作用仍有待进一步研究阐明。本研究发现，LAD1在多西他赛耐药的前列腺癌细胞中呈高表达状态，而经多西他赛治疗后的肿瘤样本中，LAD1的表达水平显著下调。此外，前列腺癌组织中LAD1的表达水平显著高于正常组织，且LAD1高表达与前列腺癌患者的不良临床结局显著相关。进一步分析显示，前列腺癌组织中LAD1的高表达还与参与肿瘤细胞增殖及侵袭行为的基因表达水平呈显著相关性。综上，本研究数据表明，LAD1有望成为前列腺癌患者潜在的预后标志物。