Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer

Oct 15, 2018Journal of cellular physiology

Abnormal levels of SNHG15 RNA linked to liver spread and lower survival in colorectal cancer

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Abstract

High expression levels of lnc-SNHG15 are associated with lymph-node and liver metastasis in colorectal cancer.

Twenty-three lncRNAs were found to be upregulated and fourteen downregulated in liver metastases compared to primary colorectal cancer and adjacent normal mucosa.
In a test set, high expression of lnc-SNHG15 was confirmed in both primary colorectal cancer lesions and liver metastases.
The expression of lnc-SNHG15 correlated significantly with lymph-node and liver metastasis in an expanded validation set of 91 patients.
Patients with high lnc-SNHG15 expression had a shorter median overall survival compared to those with low expression (30.7 vs. 35.2 months).
Overexpression of lnc-SNHG15 may serve as an independent predictor of poor prognosis in colorectal cancer patients.

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Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value. Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT-PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc-small-nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set. Furthermore, in the expanded validation set, high expression of lnc-SNHG15 was significantly associated with lymph-node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA-SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003). Multivariate analyses demonstrated that lncRNA-SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc-SNHG15 overexpression was significantly associated with CLM and high-expression of lnc-SNHG15 in CRC was an independent predictor of poor survival.

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Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer

Abstract

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