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Derlin-1高表达与中国汉族人群膀胱癌的恶性程度相关。

High Expression of Derlin-1 Is Associated with the Malignancy of Bladder Cancer in a Chinese Han Population.

作者信息

Wu Ziyu, Wang Chao, Zhang Zhan, Liu Wenlou, Xu Hengsen, Wang Huanqiang, Wang Yun, Zhang Wei, Wang Shou-Lin

机构信息

School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, People's Republic of China.

Department of Urology, Huai'an Hospital Affiliated with Xuzhou Medical University, Huai'an, People's Republic of China.

出版信息

PLoS One. 2016 Dec 15;11(12):e0168351. doi: 10.1371/journal.pone.0168351. eCollection 2016.

Abstract

Derlin-1 is overexpressed in various types of solid tumors and has an important function in cancer progression. However, its expression pattern in and association with the clinicopathological characteristics of human bladder cancer remain unclear. In the present study, 3 pairs of fresh samples of bladder cancer tissue and paracancerous tissue were first detected by liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to screen for differentially expressed proteins. Following bioinformatics analysis and assessments by qRT-PCR and western blotting, Derlin-1 was selected as a candidate protein and was then validated in samples from patients with bladder cancer by immunohistochemistry and western blotting. The results showed that the bladder cancer tissues exhibited higher levels of Derlin-1 expression than the paracancerous tissues (P < 0.05). Positive expression of Derlin-1 was significantly correlated with tumor stage, histological grade, and lymph node metastasis (P < 0.001) but was not correlated with other clinicopathological parameters including patient age (P = 0.758) and gender (P = 0.831). Besides, Derlin-1 was highly expressed in BC cell lines (um-uc-3 and T24), and the interference of Derlin-1 could reverse EMT progression, inhibit the tumor migration and invasion in T24 cells. Further, patients with positive Derlin-1 expression had shorter overall survival than those with negative expression (P < 0.001). Taken together, our results demonstrated that Derlin-1 was overexpressed in bladder cancer and was associated with the malignancy of bladder cancer.

摘要

Derlin-1在多种实体瘤中过度表达,在癌症进展中发挥重要作用。然而,其在人类膀胱癌中的表达模式及其与临床病理特征的关系仍不清楚。在本研究中,首先通过液相色谱串联质谱法(UPLC-MS/MS)检测3对膀胱癌组织和癌旁组织的新鲜样本,以筛选差异表达蛋白。经过生物信息学分析以及qRT-PCR和蛋白质印迹法评估后,选择Derlin-1作为候选蛋白,然后通过免疫组织化学和蛋白质印迹法在膀胱癌患者样本中进行验证。结果显示,膀胱癌组织中Derlin-1的表达水平高于癌旁组织(P < 0.05)。Derlin-1的阳性表达与肿瘤分期、组织学分级和淋巴结转移显著相关(P < 0.001),但与包括患者年龄(P = 0.758)和性别(P = 0.831)在内的其他临床病理参数无关。此外,Derlin-1在膀胱癌细胞系(um-uc-3和T24)中高表达,干扰Derlin-1可逆转EMT进程,抑制T24细胞的肿瘤迁移和侵袭。此外,Derlin-1表达阳性的患者总生存期短于表达阴性的患者(P < 0.001)。综上所述,我们的结果表明Derlin-1在膀胱癌中过度表达,并与膀胱癌的恶性程度相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8815/5158059/4d413f0321a5/pone.0168351.g001.jpg

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