High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer

Christina Siesing; Halfdan Sorbye; Anca Dragomir; Per Pfeiffer; Camilla Qvortrup; Fredrik Pontén; Karin Jirström; Bengt Glimelius; Jakob Eberhard

doi:10.1371/journal.pone.0182512

High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer

PLoS One. 2017 Aug 11;12(8):e0182512. doi: 10.1371/journal.pone.0182512. eCollection 2017.

Authors

Christina Siesing¹, Halfdan Sorbye², Anca Dragomir³, Per Pfeiffer⁴, Camilla Qvortrup⁴, Fredrik Pontén³, Karin Jirström¹, Bengt Glimelius⁵, Jakob Eberhard¹

Affiliations

¹ Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
² Department of Oncology, Haukeland University Hospital and Department of Clinical Science, University of Bergen, Bergen, Norway.
³ Section of Pathology, Uppsala university Hospital and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁴ Department of Oncology, Odense University Hospital, Odense, Denmark.
⁵ Department of Immunology, Genetics and Pathology, Section of Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.

Abstract

Background: High expression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC) as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy.

Methods: Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan-Meier analysis and Cox regression proportional hazards models were used to access the impact of RBM3 expression on overall survival (OS) and progression-free survival (PFS).

Results: High RBM3 expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.50-0.90 and HR 0.66, 95% CI 0.48-0.91, respectively). PFS was significantly longer in patients with high RBM3 expression who had received first-line oxaliplatin based treatment, compared to those who had received irinotecan based treatment, both regarding nuclear and cytoplasmic expression (p-value 0.020 and 0.022 respectively).

Conclusion: High RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

MeSH terms

Aged
Cell Nucleus / metabolism
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / pathology*
Disease-Free Survival
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate*
Male
Neoplasm Metastasis
Organoplatinum Compounds / therapeutic use*
Oxaliplatin
Prognosis
Proportional Hazards Models
RNA-Binding Proteins / metabolism*
Treatment Outcome

Substances

Organoplatinum Compounds
RBM3 protein, human
RNA-Binding Proteins
Oxaliplatin

Grants and funding

This study was supported by grants from the Swedish Research Council, (KJ, JE), the Swedish and Norwegian Cancer Society, (BG, HS), the Swedish Government Grant for Clinical Research, (KJ), the Kamprad Family Foundation, (JE), Knut and Alice Wallenberg Foundation, (FP), the Gunnar Nilsson Cancer Foundation, (KJ), Lund University Faculty of Medicine, (KJ), and the Lund University Hospital Research Grants (KJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.