Karnevi Emelie, Dror Liv Ben, Mardinoglu Adil, Elebro Jacob, Heby Margareta, Olofsson Sven-Erik, Nodin Björn, Eberhard Jakob, Gallagher William, Uhlén Mathias, Jirström Karin
Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
Science for Life Laboratory, KTH, Royal Institute of Technology, Stockholm, Sweden.
Oncotarget. 2017 Dec 15;9(5):6188-6200. doi: 10.18632/oncotarget.23486. eCollection 2018 Jan 19.
Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumors with dismal prognosis, partially due to lack of reliable targetable and predictive biomarkers. RNA-binding motif protein 3 (RBM3) has previously been shown to be an independent prognostic and predictive biomarker in several types of cancer. Herein, we examined the prognostic value of RBM3 in periampullary adenocarcinoma, as well as the effects following RBM3 suppression in pancreatic cancer cells . RBM3 mRNA levels were examined in 176 pancreatic cancer patients from The Cancer Genome Atlas. Immunohistochemical expression of RBM3 was analyzed in tissue microarrays with primary tumors and paired lymph node metastases from 175 consecutive patients with resected periampullary adenocarcinoma. Pancreatic cancer cells were transfected with anti-RBM3 siRNA and the influence on cell viability following chemotherapy, transwell migration and invasion was assessed. The results demonstrated that high mRNA-levels of RBM3 were significantly associated with a reduced overall survival ( = 0.026). RBM3 protein expression was significantly higher in lymph node metastases than in primary tumors ( = 0.005). High RBM3 protein expression was an independent predictive factor for the effect of adjuvant chemotherapy and an independent negative prognostic factor in untreated patients ( for interactio 0.003). After siRNA suppression of RBM3 , pancreatic cancer cells displayed reduced migration and invasion compared to control, as well as a significantly increased resistance to chemotherapy. In conclusion, the strong indication of a positive response predictive effect of RBM3 expression in pancreatic cancer may be highly relevant in the clinical setting and merits further validation.
壶腹周围腺癌，包括胰腺癌，是一组预后不佳的异质性肿瘤，部分原因是缺乏可靠的可靶向和预测性生物标志物。RNA结合基序蛋白3（RBM3）此前已被证明是几种癌症中的独立预后和预测生物标志物。在此，我们研究了RBM3在壶腹周围腺癌中的预后价值，以及RBM3抑制对胰腺癌细胞的影响。对来自癌症基因组图谱的176例胰腺癌患者的RBM3 mRNA水平进行了检测。对175例连续接受壶腹周围腺癌切除术的患者的原发性肿瘤和配对淋巴结转移的组织芯片进行了RBM3免疫组化表达分析。用抗RBM3 siRNA转染胰腺癌细胞，并评估化疗、Transwell迁移和侵袭后对细胞活力的影响。结果表明，RBM3的高mRNA水平与总生存期缩短显著相关（P = 0.026）。RBM3蛋白表达在淋巴结转移中显著高于原发性肿瘤（P = 0.005）。高RBM3蛋白表达是辅助化疗效果的独立预测因素，也是未治疗患者的独立阴性预后因素（交互作用P = 0.003）。RBM3被siRNA抑制后，胰腺癌细胞与对照组相比迁移和侵袭减少，对化疗的耐药性也显著增加。总之，RBM3表达在胰腺癌中具有阳性反应预测作用的强烈迹象在临床环境中可能高度相关，值得进一步验证。
