SLUG转录因子：胃肠道间质瘤中的一种促生存和预后因子。
SLUG transcription factor: a pro-survival and prognostic factor in gastrointestinal stromal tumour.
作者信息
Pulkka Olli-Pekka, Nilsson Bengt, Sarlomo-Rikala Maarit, Reichardt Peter, Eriksson Mikael, Hall Kirsten Sundby, Wardelmann Eva, Vehtari Aki, Joensuu Heikki, Sihto Harri
机构信息
Laboratory of Molecular Oncology, Translational Cancer Biology Research Program, Department of Oncology, University of Helsinki, P.O Box 63, FI-00014 University of Helsinki, Helsinki, Finland.
Department of Surgery, Sahlgrenska University Hospital, Gothenburg SE-41345, Sweden.
出版信息
Br J Cancer. 2017 Apr 25;116(9):1195-1202. doi: 10.1038/bjc.2017.82. Epub 2017 Mar 23.
BACKGROUND
The SLUG transcription factor has been linked with the KIT signalling pathway that is important for gastrointestinal stromal tumour (GIST) tumourigenesis. Its clinical significance in GIST is unknown.
METHODS
Influence of SLUG expression on cell proliferation and viability were investigated in GIST48 and GIST882 cell lines. The association between tumour SLUG expression in immunohistochemistry and recurrence-free survival (RFS) was studied in two clinical GIST series, one with 187 patients treated with surgery alone, and another one with 313 patients treated with surgery and adjuvant imatinib.
RESULTS
SLUG downregulation inhibited cell proliferation, induced cell death in both cell lines, and sensitised GIST882 cells to lower imatinib concentrations. SLUG was expressed in 125 (25.0%) of the 500 clinical GISTs evaluated, and expression was associated with several factors linked with unfavourable prognosis. SLUG expression was associated with unfavourable RFS both when patients were treated with surgery alone (HR=3.40, 95% CI=1.67-6.89, P=0.001) and when treated with surgery plus adjuvant imatinib (HR=1.83, 95% CI=1.29-2.60, P=0.001).
CONCLUSIONS
GIST patients with high tumour SLUG expression have unfavourable RFS. SLUG may mediate pro-survival signalling in GISTs.
背景
SLUG转录因子与对胃肠道间质瘤（GIST）肿瘤发生至关重要的KIT信号通路相关。其在GIST中的临床意义尚不清楚。
方法
在GIST48和GIST882细胞系中研究SLUG表达对细胞增殖和活力的影响。在两个临床GIST系列中研究免疫组织化学中肿瘤SLUG表达与无复发生存期（RFS）之间的关联，一个系列有187例仅接受手术治疗的患者，另一个系列有313例接受手术及辅助伊马替尼治疗的患者。
结果
SLUG下调抑制细胞增殖，在两种细胞系中诱导细胞死亡，并使GIST882细胞对较低浓度的伊马替尼敏感。在评估的500例临床GIST中，125例（25.0%）表达SLUG，其表达与几个与不良预后相关的因素有关。当患者仅接受手术治疗时（HR=3.40，95%CI=1.67-6.89，P=0.001）以及接受手术加辅助伊马替尼治疗时（HR=1.83，95%CI=1.29-2.60，P=0.001），SLUG表达均与不良RFS相关。
结论
肿瘤SLUG高表达的GIST患者RFS不良。SLUG可能介导GIST中的促生存信号传导。
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