Mao Changlin, Dong Wei, Lu Jiaju, Zhang Zhao, Wu Hongliang, Ghavamian Armin, Bi Dongbin, Gao Pei, Liu Zhao, Ding Sentai
Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China.
Department of Urology, Shandong Provincial Hospital West Branch, Jinan, Shandong, 250000, People's Republic of China.
Cancer Manag Res. 2021 Aug 12;13:6377-6387. doi: 10.2147/CMAR.S320490. eCollection 2021.
Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on βKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa.
Western blotting was used to determine the expression of βKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of βKlotho and ELK4 in the proliferation of PCa cells. The expression of βKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson's χ2 test and Fisher's exact test were performed to investigate the associations among βKlotho, ELK4 and various clinical factors. Kaplan-Meier curves and Cox regression model were established to reveal the correlation among βKlotho, ELK4 expression and the prognosis of patients.
βKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. βKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher βKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, βKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa.
βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.
前列腺癌(PCa)是全球男性中第二常见的恶性肿瘤。尽管在过去几十年中诊断和治疗取得了显著进展,但PCa的预后期望仍不尽人意。为了改善PCa的预后预测,需要更具特异性的生物标志物。在这项回顾性研究中,我们聚焦于βKlotho和ETS样转录因子4(ELK4),旨在确定PCa潜在的预后生物标志物。
采用蛋白质免疫印迹法检测C4-2B和PC3前列腺癌细胞系中βKlotho、ELK4和PARP的表达。应用CCK-8法和集落形成试验检测βKlotho和ELK4在前列腺癌细胞增殖中的作用。通过免疫化学法测定PCa组织样本中βKlotho和ELK4的表达。采用Pearson卡方检验和Fisher精确检验研究βKlotho、ELK4与各种临床因素之间的关联。建立Kaplan-Meier曲线和Cox回归模型,以揭示βKlotho、ELK4表达与患者预后之间的相关性。
βKlotho过表达下调ELK4表达,诱导C4-2B和PC3细胞凋亡并抑制其增殖,而ELK4过表达可逆转这些作用。PCa组织样本中βKlotho表达与ELK4表达呈负相关,较高的βKlotho表达与较低的Gleason评分、无远处转移和较低的前列腺特异性抗原(PSA)水平相关。相反,较高的ELK4表达与远处转移和较高的PSA水平相关。此外,βKlotho和ELK4均被认为是PCa患者预后的独立因素。
βKlotho通过下调ELK4抑制前列腺癌细胞增殖。βKlotho和ELK4的表达均与PCa的预后相关,它们可能作为潜在的生物标志物用于随访监测和预后评估。