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Aberrant expression of long noncoding RNAs in colorectal cancer with liver metastasis

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Tumor Biology

Abstract

Long noncoding RNA (lncRNA) plays a crucial role in the regulation of various cellular processes and human diseases. However, little is known about the role of lncRNAs in colorectal liver metastasis (CLM). In the present study, we aimed to determine whether lncRNAs are differentially expressed in CLM tissue and to further assess their clinical value. lncRNA arrays were employed to screen for differentially expressed lncRNAs in colorectal cancer (CRC) tissues with synchronous, metachronous, or nonliver metastasis. Based on bioinformatics data, a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was performed to identify target lncRNAs in an expanded set of CRC samples with various subtypes of liver metastasis. The relationships between the target lncRNAs and the clinical characteristics and patient prognosis were further analyzed. After determining the expression profile of lncRNAs (n = 1332) in CLM tissue, 40 differentially expressed lncRNAs that were potentially related to CLM were selected for further examination in an expanded set of clinical samples, and three novel target lncRNAs, termed lncRNA-CLMAT1-3, were verified. High lncRNA-CLMAT3 expression strongly correlated with liver metastasis (P = 0.03) and lymph node metastasis (P = 0.009). Moreover, patients displaying high lncRNA-CLMAT3 expression exhibited a shorter median overall survival duration than those displaying low lncRNA-CLMAT3 expression (30.7 vs. 35.2 months, P = 0.007). Multivariate analysis demonstrated that the lncRNA-CLMAT3 expression level is an independent prognostic factor (hazard ratio 2.05, P = 0.02) after adjusting for other known prognostic factors. lncRNA-CLMAT3 over-expression was significantly associated with CLM and was an independent predictor of poor survival for patients with CRC.

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Acknowledgments

We thank the National Natural Science Foundation of China (No. 81372315), Shanghai medical guide project (134119a4800) and Shanghai Scientific Research Plan Project (No. 13JC1401601) for providing funding supports.

Conflicts of interest

None

Authors’ contributions

Le-chi Ye and Li Ren performed the molecular genetics experiments, participated in the sequence alignment, and drafted the manuscript. Jun-jun Qiu participated in the sequence alignment. Tao Chen, De-xiang Zhu, and Wen-ju Chang participated in the design of the study and performed the statistical analysis. Jianmin Xu, Li Ren, and Ye Wei conceived of the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China

    Le-chi Ye & Shi-xu Lv

  2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200000, China

    Le-chi Ye, Li Ren, De-xiang Zhu, Tao Chen, Wen-ju Chang & Jianmin Xu

  3. Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China

    Jun-jun Qiu

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  1. Le-chi Ye
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Correspondence to Jianmin Xu.

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Li-chi Ye and Li Ren contributed equally to this work.

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Figure S1

Overview of the lncRNA microarray analysis results. Heat maps were generated based on hierarchical cluster analysis to display the differentially expressed lncRNAs (>2 fold-change in expression and P < 0.01) between the SLM and NCR samples (A), the MLM and NLM samples (B), the SLM and MLM samples (C), or the SLM and NLM samples (D). Abbreviations: CRC, colorectal cancer; NCR, normal colorectum; NLM, CRC with no liver metastasis; MLM, CRC with metachronous liver metastasis; SLM, CRC with synchronous liver metastasis. (JPEG 185 kb)

Figure S2

Validation of the microarray results. Five lncRNAs were randomly selected from the microarray data for validation via a qRT-PCR assay. (JPEG 1234 kb)

Figure S3

lncRNA-CLMAT3 (as indicated by the red arrow) neighbors the SPARC gene according to the data from the UCSC genome browser. (JPEG 372 kb)

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Ye, Lc., Ren, L., Qiu, Jj. et al. Aberrant expression of long noncoding RNAs in colorectal cancer with liver metastasis. Tumor Biol. 36, 8747–8754 (2015). https://doi.org/10.1007/s13277-015-3627-4

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  • DOI: https://doi.org/10.1007/s13277-015-3627-4

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