Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study.
Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study.
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DOI：
10.1186/1471-2407-14-214
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发表时间：
2014-03-20
期刊：
影响因子：
3.8
通讯作者：
Stoehr R
中科院分区：
文献类型：
--
作者：
Rogler A;Hoja S;Giedl J;Ekici AB;Wach S;Taubert H;Goebell PJ;Wullich B;Stöckle M;Lehmann J;Petsch S;Hartmann A;Stoehr R
70%的膀胱肿瘤倾向于复发，需要加强监测，一部分肿瘤进展为肌肉浸润性和转移性疾病。然而，仍然很难为每个个体患者找到适当的治疗方法，因为它是一种非常异质性的疾病，并且仍然缺少可靠的生物标志物。在我们的研究中，我们在关键染色体区域8 p中寻找新的靶基因，并研究膀胱癌中潜在的肿瘤抑制基因候选者MTUS 1/ATIP。MTUS 1被确定为最有希望的目标基因在8 p的aCGH分析与19乳头状膀胱肿瘤。使用85个乳头状和236个晚期膀胱肿瘤的免疫组化和功能实验进一步验证与膀胱癌的相关性。Kaplan-Meier分析和多变量Cox回归将总生存期（OS）和疾病特异性生存期（DSS）作为MTUS 1/ATIP表达的函数。双变量相关性研究MTUS 1/ATIP表达，患者特征和组织病理学之间的关联。在细胞系中分析MTUS 1表达，并在RT 112中过表达，其中测量对活力、增殖和迁移的影响。MTUS 1蛋白表达在近50%的乳头状和晚期膀胱癌中丢失。然而，生存率仅在晚期癌症中受到影响，其中MTUS 1的丢失与不良OS和DSS相关。在该队列中，MTUS 1表达与组织学亚型也存在显著相关性：在所有微乳头状肿瘤中均检测到阳性表达，在浆细胞样尿路上皮癌亚组中检测到异常核染色。MTUS 1在所有研究的膀胱细胞系中表达，并且在RT 112中过表达导致活力显著降低。MTUS 1是培养的膀胱癌细胞和晚期膀胱肿瘤中的肿瘤抑制基因。它可能代表染色体8 p上的一个新靶基因，可作为晚期膀胱癌患者的独立预后因子。本研究的局限性在于回顾性数据分析。因此，研究结果应与前瞻性晚期膀胱肿瘤队列进行验证。
Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be used as an independent prognostic factor for advanced bladder cancer patients. The limitation of the study is the retrospective data analysis. Thus, findings should be validated with a prospective advanced bladder tumour cohort.
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影响因子：
8.8
作者：
Munksgaard, P. P.;Mansilla, F.;Eskildsen, A-S Brems;Fristrup, N.;Birkenkamp-Demtroder, K.;Ulhoi, B. P.;Borre, M.;Agerbaek, M.;Hermann, G. G.;Orntoft, T. F.;Dyrskjot, L.
通讯作者：
Dyrskjot, L.
影响因子：
8.8
作者：
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Summerhayes, I. C.
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影响因子：
5.8
作者：
OTTESEN, SS;AHRENKIEL, V;KIELER, J
通讯作者：
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作者：
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