Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases

Abstract

BackgroundDespite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood.MethodsIn order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver).ResultsThe gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells.ConclusionsThe present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users.

Tumor Heterogeneity in Primary Colorectal Cancer and Corresponding Metastases. Does the Apple Fall Far From the Tree?

“…In addition, the capability to metastasize does not rely on alterations of only a few genes, exceptionally found in metastasized tumors, rather it is the combination of different genes and the amount of gene expression alteration that fosters metastatic spread [ 72 ]. Other studies confirmed high levels of similarity between primary CRCs and matched metastases on the RNA level, and primary tumors preferentially group with their paired liver metastasis in hierarchical clustering [ 73 , 74 ]. These conclusions are in line with the findings on DNA level.…”

Transcriptome analysis in primary colorectal cancer tissues from patients with and without liver metastases using next‐generation sequencing

“…A and B). We then removed genes with extremely low FPKM (FPKM < 0.5) values in both the T and C groups on that basis . Therefore, 22 upregulated and 73 downregulated DEGs were included after filtering (Table ).…”

“…To quantify each DEG, the fragments per kb per million fragments (FPKM) method are adopted . To calculate the expression level, the following formula was used:…”

Modelling RNA‐Seq data with a zero‐inflated mixture Poisson linear model

“…Nagalakshmi et al (2008) and Wilhelm et al (2008) confirmed its ability to identify both known and unknown transcripts. Recent works, such as Kekeeva et al (2016), Lee et al (2016), and Xu, Sun, Hang, Gao, and Hu (2016), applied this technique to search for novel fusion genes in cancer.…”