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.

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

Grant support

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.