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

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

doi:10.1371/journal.pone.0182512

Abstract

BackgroundHigh 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.MethodsImmunohistochemical 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).ResultsHigh 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).ConclusionHigh RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

Highlights

Colorectal cancer (CRC) is the third most common cancer in the world affecting 1.4 million people each year [1]
High RNA-binding motif protein 3 (RBM3) expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged overall survival (OS)
progression-free survival (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)

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer in the world affecting 1.4 million people each year [1]. Chemotherapy for mCRC is based on 5-fluorouracil (5-FU) with the addition of either irinotecan or oxaliplatin. Irinotecan combined with 5-FU, as in FOLFIRI, increases progression-free survival (PFS) and overall survival (OS) [7]. First-line chemotherapy with irinotecan based chemotherapy or oxaliplatin based chemotherapy seem to give a similar overall survival and no data have shown preference for one schedule over the other as first-line treatment [11]. 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 platinumbased 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

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