Lee Myung-Shin, Lee Jisu, Lee Suhyuk, Yoo Seung-Min, Kim Joo Heon, Kim Won Tae, Kim Wun-Jae, Park Jinsung
Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South Korea.
Department of Pathology, Eulji University School of Medicine, Daejeon, South Korea.
Oncotarget. 2018 Jan 8;9(8):7961-7974. doi: 10.18632/oncotarget.24091. eCollection 2018 Jan 30.
Heat shock protein 27 (HSP27) is highly expressed in many cancers, and its prognostic and predictive value has been reported. HSP27 knockdown using siRNA or OGX-427 (an anti-sense oligonucleotide sequence targeting HSP27) is reported to have anti-cancer effects and to enhance chemosensitivity of cancer cells to chemotherapeutic agents. However, conflicting results have been reported regarding the clinical significance of HSP27 in bladder cancer (BC). Furthermore, long-term suppression of HSP27 has not been investigated in BC. In this study, we investigated the association between HSP27 expression and BC characteristics in 132 BC patient samples, as well as its prognostic value to determine the potential of HSP27 as a clinical biomarker. Additionally, we applied five different shRNAs targeting HSP27 in three invasive BC cell lines to analyze the long-term knockdown effects of HSP27. Our study revealed a significant association between HSP27 expression and adverse pathological characteristics such as high-stage and -grade BC. However, HSP27 expression was not associated with clinical outcomes such as tumor recurrence, progression, and patient survival. Interestingly, although our shRNAs had obvious knockdown effects on HSP27 in BC cells, we did not find consistent effects on apoptosis of BC cells or chemotherapeutic sensitivity of BC cells to cisplatin. Therefore, although HSP27 may be a predictor of adverse pathological characteristics in BC, its role as a prognostic biomarker and therapeutic target seems to be limited.
热休克蛋白27（HSP27）在多种癌症中高表达，其预后和预测价值已有报道。据报道，使用小干扰RNA（siRNA）或OGX - 427（一种靶向HSP27的反义寡核苷酸序列）敲低HSP27具有抗癌作用，并能增强癌细胞对化疗药物的化学敏感性。然而，关于HSP27在膀胱癌（BC）中的临床意义，已有相互矛盾的报道。此外，尚未在膀胱癌中研究HSP27的长期抑制作用。在本研究中，我们调查了132例膀胱癌患者样本中HSP27表达与膀胱癌特征之间的关联，以及其预后价值，以确定HSP27作为临床生物标志物的潜力。此外，我们在三种侵袭性膀胱癌细胞系中应用了五种靶向HSP27的不同短发夹RNA（shRNA），以分析HSP27的长期敲低效果。我们的研究揭示了HSP27表达与不良病理特征（如高分期和高级别膀胱癌）之间存在显著关联。然而，HSP27表达与肿瘤复发、进展和患者生存等临床结局无关。有趣的是，尽管我们的shRNA对膀胱癌细胞中的HSP27有明显的敲低作用，但我们并未发现对膀胱癌细胞凋亡或膀胱癌细胞对顺铂的化疗敏感性有一致的影响。因此，尽管HSP27可能是膀胱癌不良病理特征的一个预测指标，但其作为预后生物标志物和治疗靶点的作用似乎有限。
