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Translational study reveals a two-faced role of RBM3 in pancreatic cancer and suggests its potential value as a biomarker for improved patient stratification
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
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2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 5, p. 6188-6200Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Impact Journals LLC , 2018. Vol. 9, no 5, p. 6188-6200
Keywords [en]
Pancreatic cancer, Periampullary cancer, Prediction, Prognosis, RBM3, antineoplastic agent, cyclooxygenase 2, gemcitabine, interleukin 8, messenger RNA, RNA binding motif protein 3, RNA binding protein, small interfering RNA, unclassified drug, adult, aged, Article, cancer adjuvant therapy, cancer prognosis, cell migration, cell motility, cell viability, cohort analysis, controlled study, drug resistance, drug sensitivity, female, fetus, human, human cell, human tissue, in vitro study, lymph node metastasis, major clinical study, male, overall survival, pancreas cancer, pancreatic cancer cell line, pancreaticoduodenectomy, periampullary adenocarcinoma, predictive value, protein expression, protein function, recurrence free survival, retrospective study, translational research, tumor invasion
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Clinical Medicine
Identifiers
URN: urn:nbn:se:kth:diva-223186DOI: 10.18632/oncotarget.23486Scopus ID: 2-s2.0-85040697313OAI: oai:DiVA.org:kth-223186DiVA, id: diva2:1186350
Note

Export Date: 13 February 2018; Article; Correspondence Address: Jirström, K.; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Skåne University HospitalSweden; email: karin.jirstrom@med.lu.se. QC 20180228

Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-02-28Bibliographically approved

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Mardinoglu, AdilUhlén, Mathias

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