Pathological significance and prognostic role of LATS2 in prostate cancer.
Pathological significance and prognostic role of LATS2 in prostate cancer.
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DOI：
10.1002/pros.24226
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发表时间：
2021-11
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影响因子：
--
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中科院分区：
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大肿瘤抑制因子2（LATS 2）是Hippo通路的重要调节因子，在细胞存活和行为中起着至关重要的作用。在此，我们评估了LATS 2在前列腺癌（PC）中的病理作用，这方面的信息很少。在两种PC细胞系（LNCaP和PC 3）中评价了响应siRNA介导的敲低（KD）LATS 2表达的细胞增殖、迁移和侵袭。对204例PC患者标本中LATS 2的表达进行了免疫组化研究，并研究了其表达与临床病理特征、增殖指数（PI;使用抗KI-67抗体测量）和生化复发（BCR）之间的关系。LATS 2的KD增加LNCaP细胞的生长、迁移和侵袭，并且仅增加PC 3细胞的迁移。LATS 2的表达与肿瘤的分级、T、N、M分期及PI呈负相关。此外，LATS 2的表达是新辅助激素治疗和无BCR生存期的组织学效应的有用预测因子。包括临床病理特征的多因素分析模型显示LATS 2阴性表达者BCR的风险显著增高（OR = 2.95，P < 0.001）。LATS 2在PC中起肿瘤抑制剂的作用。LATS 2表达是BCR的有用预测因子。LATS 2相关活性可能依赖于PC细胞的雄激素依赖性。因此，我们认为LATS 2可能是PC患者潜在的治疗靶点和有用的预后预测因子。
Large tumor suppressor 2 (LATS2) is an important regulator of the Hippo pathway and it plays crucial roles in cell survival and behaviors. Herein, we evaluated the pathological roles of LATS2 in prostate cancer (PC), for which very little information is available. Cell proliferation, migration, and invasion in response to the siRNA‐mediated knockdown (KD) LATS2 expression were evaluated in two PC cell lines (LNCaP and PC3). The expression of LATS2 in specimens from 204 PC patients was investigated immunohistochemically, and the relationships between its expression and clinicopathological features, proliferation index (PI; measured using an anti‐KI‐67 antibody), and biochemical recurrence (BCR) were investigated. KD of LATS2 increased the growth, migration, and invasion in LNCaP cells and only increased migration in PC3 cells. The expression of LATS2 was negatively associated with the grade group, T, N, M stage, and PI. In addition, the expression of LATS2 was a useful predictor of the histological effects of neoadjuvant hormonal therapy and BCR‐free survival periods. A multivariate analysis model including clinicopathological features showed that negative expression of LATS2 had a significantly higher risk of BCR (odds ratio = 2.95, P < 0.001). LATS2 acts as a tumor suppressor in PC. LATS2 expression is a useful predictor for BCR. LATS2‐related activities are possibly dependent on the androgen‐dependency of PC cells. Therefore, we suggest that LATS2 could be a potential therapeutic target and a useful predictor for outcome in patients with PC.
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