Abstract
Liver metastasis is the primary cause of death for colorectal cancer (CRC) patients. To investigate the prognostic value of long non-coding RNAs (lncRNAs) on colorectal liver metastases, quantitative reverse-transcriptase PCR (quantitative RT-PCR) was performed on 15 lncRNAs in 51 stage IV CRC with liver metastases and 57 stage I/II CRC specimens. The expression levels of four lncRNAs (GAS5, H19, MEG3 and Yiya) were significantly different between liver metastases and primary tumors of stage IV CRC patients. Furthermore, the high expression levels of GAS5 and Yiya were significantly associated with future occurrence of liver metastases in early stage CRC patients. Kaplan-Meier analysis showed that the high expression levels of GAS5 or Yiya were correlated with poor prognosis of early stage CRC patients (p = 0.0206 and 0.0005 for GAS5 and Yiya, respectively). Yiya expression was proved to be an independent prognostic indicator of colorectal liver metastases in a multivariate analysis (relative risk = 10.7; p < 0.0001). Our study revealed that GAS5 and Yiya were promising prognostic biomarkers of liver metastases for early stage CRC patients.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, with an estimated 1.4 million cases and 693,900 deaths occurring in 2012 [1]
Quantification correlation of three non-overlapping short amplicons for each of the 15 collected long non-coding RNAs (lncRNAs) and β-actin gene was determined in 51 stage IV colorectal cancer (CRC) specimens and corresponding liver metastases (Supplementary Table S1)
Expression levels of 13 lncRNAs were compared between primary stage IV CRC and matched liver metastases in 51 pairs of samples (Table 1)
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, with an estimated 1.4 million cases and 693,900 deaths occurring in 2012 [1]. The five-year survival rate for localized CRC patients is up to 90% [3], while it is only 6% for stage IV CRC with distant metastases [4]. Survival time of early stage CRC patients without lymph node or distant metastases varies widely after surgical resections. Most patients do not present hepatic metastases within five years while the others show metastatic deposits in liver soon. This observation emphasizes the clinical and molecular heterogeneity in CRC [4]. Finding out the factors involved in this heterogeneity will assist clinical intervention and treatment against liver metastases for early stage CRC patients
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