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Date: 08 Jun 2014

Low expression of novel lncRNA RP11-462C24.1 suggests a biomarker of poor prognosis in colorectal cancer

Abstract

Long noncoding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules, which were involved in a broad range of biological processes and complex diseases. Research on lncRNAs may shed light on tumorigenesis and progression of colorectal cancer (CRC). The purpose of the present study was to identify lncRNAs correlated with CRC and then investigate their potential functions. We selected 92 patients for this prospective study and then collected the tumor samples and clinical records. First, the global lncRNA expression profiles in tumor and adjacent normal tissues of patients with non-metastatic CRC and patients with metastatic CRC were measured by microarray assay. Then, a noteworthy lncRNAs RP11-462C24.1 whose function was previously unknown was explored in detail on the aspect of the association of its expression level and clinicopathological features of CRC and patients’ survival. We found that RP11-462C24.1 expression level was lower in cancer tissues compared with adjacent normal samples (P < 0.001). Furthermore, its expression level was lower in CRC patients with metastasis than those without metastasis (P = 0.049). That is, RP11-462C24.1 expression level decreased as the malignant degree of CRC increased. In addition, low expression of RP11-462C24.1 significantly correlated with more distant metastasis (P = 0.011). The areas under ROC curves were 0.78 and 0.65 for RP11-462C24.1, distinguishing CRC from normal tissue and distinguishing CRC without metastasis from CRC with metastasis, respectively. Multivariate analysis identified that RP11-462C24.1 was an independent predictor for patients prognosis (P = 0.005). Furthermore, Kaplan–Meier analysis showed that patients with low expression of RP11-462C24.1 had a poor disease-free survival (P < 0.001). This is the first study that correlates RP11-462C24.1 expression profile with malignancy grade in human CRC. Our results showed that RP11-462C24.1 could be a potential novel prognostic marker for CRC, and thus, provided a new strategy for CRC diagnosis. Meanwhile, our findings indicated the potential roles of RP11-462C24.1 in tumorigenesis and progression of CRC, which gave a clue for future studies.

Debing Shi and Hongtu Zheng contribute equally to this study.