ROR1 expression as a biomarker for predicting prognosis in patients with colorectal cancer.

Jian-Kang Zhou,Carlo M Croce,Xue-Sha Liu,Cheng-Lin Guo,Lunxu Liu,Yu-Zhu Zheng,Yong Peng,Rui Ma,Qiheng Gou

doi:10.18632/oncotarget.15860

Abstract

There is a lack of reliable prognosis biomarker in the current treatment of colorectal cancer. The receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is overexpressed and associated with poor prognosis in certain tumors. This study aimed to explore the prognostic significance of ROR1 in colorectal cancer. Western blot analysis and immunohistochemistry showed that the expression of ROR1 in colorectal cancer was significantly higher than that in the adjacent normal tissues. ROR1 expression was positively associated with the clinical stage and lymph-node metastasis (p < 0.01). Kaplan-Meier survival analysis revealed that patients with higher ROR1 expression had a significantly shorter overall survival (p < 0.01). Multivariate Cox regression analysis confirmed that ROR1 is an independent prognostic marker in colorectal cancer (p = 0.002, HR = 2.08, 95% CI: 1.314–3.292). Thus, our study demonstrated that ROR1 expression is correlated with malignant attributes and may serve as a novel prognostic marker and therapeutic target for colorectal cancer.

Highlights

Colorectal cancer (CRC) accounts for 8% of all cancer-related deaths [1]
There was no change in receptor 1 (ROR1) level observed in SW480 cells, the expression of ROR1 protein significantly increased in other two investigated CRC cells, DLD-1 and HT-29, when compared with immortalized normal colon cell HCoEpiC (Figure 1D), which implied that ROR1 expression widely elevates in the CRC cells
The prognosis and treatment of CRC patients still depend on the pathological stage of tumors evaluated by American Joint Committee on Cancer (AJCC) TNM staging system [16]

Summary

Introduction

Localized CRC patients (stage I-II) are curable by surgery or radical radiotherapy, while patients at stage III-IV need systematic therapy including chemotherapy and target therapy to improve survival and minimize the possibility of relapse [2]. Lack of accurate biomarkers to identify earlystage and low-risk patients often leads to overtreatment [3]. It is of critical importance to identify diagnostic and prognostic biomarkers to improve CRC patients' survival. The pathological staging is not accurate enough to predict the recurrence. About 10-20% of stage II patients and 30-40% of stage III patients still develop tumor recurrence [5]. Microsatellite instability (MSI) is identified as a prognostic factor for early stage CRC patients [6], and KRAS is found to be a predictive marker in EGFR-targeted therapy of advanced CRC [7]. Identification of novel and specific biomarkers with clinicopathological and prognostic significance is vital for CRC management

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