Translational study reveals a two-faced role of RBM3 in pancreatic cancer and suggests its potential value as a biomarker for improved patient stratification
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Emelie Karnevi1, Liv Ben Dror1, Adil Mardinoglu2, Jacob Elebro1, Margareta Heby1, Sven-Erik Olofsson1, Björn Nodin1, Jakob Eberhard1, William Gallagher3, Mathias Uhlén2 and Karin Jirström1
1Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden
2Science for Life Laboratory, KTH, Royal Institute of Technology, Stockholm, Sweden
3UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, 31 University College Dublin, Dublin, Ireland
Karin Jirström, email: [email protected]
Keywords: RBM3, pancreatic cancer, periampullary cancer, prognosis, prediction
Received: August 02, 2017 Accepted: October 05, 2017 Published: December 15, 2017
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 in vitro. 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 in vitro 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 (p = 0.026). RBM3 protein expression was significantly higher in lymph node metastases than in primary tumors (p = 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 (p for interaction = 0.003). After siRNA suppression of RBM3 in vitro, 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.
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