Rho-GTPase activating-protein 18: a biomarker associated with good prognosis in invasive breast cancer.
Rho-GTPase activating-protein 18: a biomarker associated with good prognosis in invasive breast cancer.
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DOI：
10.1038/bjc.2017.261
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发表时间：
2017-10-10
影响因子：
8.8
通讯作者：
Rakha EA
中科院分区：
文献类型：
--
作者：
Aleskandarany MA;Sonbul S;Surridge R;Mukherjee A;Caldas C;Diez-Rodriguez M;Ashankyty I;Albrahim KI;Elmouna AM;Aneja R;Martin SG;Ellis IO;Green AR;Rakha EA
淋巴管浸润（LVI）在乳腺癌（BC）中的预后价值已在几项独立研究中得到证实。然而，识别LVI的驱动分子仍然是一项具有挑战性的任务。大规模的组织学验证的LVI的转录组学分析可以潜在地确定基因，调节LVI。采用组织学和免疫组织化学（IHC）标准，使用严格定义的LVI子集对METABRIC研究进行综合生物信息学分析。ARHGAP 18是LVI+和LVI− BC之间差异表达最多的基因之一，变化为1.8倍。在METABRIC数据集（n=1980）中评估了ARHGAP 18基因表达的预后影响，并使用bc-GenExMiner v4.0（n=2016）在线BC基因表达数据集进行了外部验证。随后，在一个大的侵袭性BC队列（n=959）中使用IHC评估ARHGAP 18蛋白表达，并进行长期随访。ARHGAP 18 mRNA表达的汇总分析显示，过度表达与更好的结局相关（P<0.001，风险比（HR）=0.82，95% CI 0.75-0.90）。ARHGAP 18蛋白在肿瘤细胞的细胞质和细胞核中表达，其表达与良好的预后变量呈正相关。胞浆表达缺失与LVI（P=0.006）、上皮-间质转化和HER+亚型（P=0.01）相关。核表达缺失与高分级、HER 2+和高Ki 67 LI相关（P=0.001）。细胞质和细胞核表达与生存率的改善呈正相关，与其他变量无关（P=0.01，HR=0.74，95%CI 0.60-87）。ARHGAP 18在转录组和蛋白水平的表达与改善患者的预后相关，其失调可能在BC的肿瘤进展和LVI发展中发挥作用。进一步评估其在BC中的潜在治疗价值是必要的。
The prognostic value of lymphovascular invasion (LVI) in breast cancer (BC) has been demonstrated in several independent studies. However, identification of driver molecules for LVI remains a challenging task. Large-scale transcriptomic profiling of histologically validated LVI can potentially identify genes that regulate LVI. Integrative bio-informatics analyses of the METABRIC study were performed utilising a subset of strictly defined LVI using histological and immunohistochemical (IHC) criteria. ARHGAP18 was among the top differentially expressed genes between LVI+ and LVI− BC with a 1.8-fold change. The prognostic impact of ARHGAP18 gene expression was assessed in the METABRIC data set (n=1980) and externally validated using the online BC gene expression data sets utilising bc-GenExMiner v4.0 (n=2016). Subsequently, ARHGAP18 protein expression was assessed on a large cohort of invasive BC (n=959) with long-term follow-up using IHC. Pooled analysis of ARHGAP18 mRNA expression showed that overexpression was associated with better outcome (P<0.001, hazard ratio (HR)=0.82, 95% CI 0.75–0.90). ARHGAP18 protein was expressed in the cytoplasm and nuclei of the tumour cells and its expression was positively associated with good prognostic variables. Lack of cytoplasmic expression showed associations with LVI (P=0.006), epithelial-mesenchymal transition and the HER+ subtype (P=0.01). Loss of nuclear expression was associated with higher grade, HER2+ and high Ki67LI (P=0.001). Cytoplasmic and nuclear expression showed a positive association with improved survival independent of other variables (P=0.01, HR=0.74, 95% CI 0.60–87). ARHGAP18 expression at transcriptomic and protein levels is associated with improved patients’ outcomes whose deregulation may play a role in tumour progression and the development of LVI in BC. Further assessment of its potential therapeutic value in BC is warranted.
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影响因子：
2.4
作者：
Song YJ;Shin SH;Cho JS;Park MH;Yoon JH;Jegal YJ
通讯作者：
Jegal YJ
影响因子：
7.3
作者：
Albasri, Abdulkader;Seth, Rashmi;Ilyas, Mohammad
通讯作者：
Ilyas, Mohammad
DOI：
10.1046/j.1524-4741.2003.09304.x
发表时间：
2003-05-01
期刊：
The breast journal
影响因子：
--
作者：
Choi, Seung-Hye;Barsky, Sanford H;Chang, Helena R
通讯作者：
Chang, Helena R
DOI：
10.1073/pnas.0607899103
发表时间：
2006-10-31
影响因子：
11.1
作者：
Zhao, Jean J.;Cheng, Hailing;Roberts, Thomas M.
通讯作者：
Roberts, Thomas M.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel