Identification of novel enriched recurrent chimeric COL7A1-UCN2 in human laryngeal cancer samples using deep sequencing

Ye Tao,Neil Gross,Xiaojiao Fan,Xu Li,Jianming Yang,Guojun Li,Yang Zhang,Zhigang Huang,Maikun Teng

doi:10.1186/s12885-018-4161-8

Abstract

BackgroundAs hybrid RNAs, transcription-induced chimeras (TICs) may have tumor-promoting properties, and some specific chimeras have become important diagnostic markers and therapeutic targets for cancer.MethodsWe examined 23 paired laryngeal cancer (LC) tissues and adjacent normal mucous membrane tissue samples (ANMMTs). Three of these pairs were used for comparative transcriptomic analysis using high-throughput sequencing. Furthermore, we used real-time polymerase chain reaction (RT-PCR) for further validation in 20 samples. The Kaplan-Meier method and Cox regression model were used for the survival analysis.ResultsWe identified 87 tumor-related TICs and found that COL7A1-UCN2 had the highest frequency in LC tissues (13/23; 56.5%), whereas none of the ANMMTs were positive (0/23; p < 0.0001). COL7A1-UCN2, generated via alternative splicing in LC tissue cancer cells, had disrupted coding regions, but it down-regulated the mRNA expression of COL7A1 and UCN2. Both COL7A1 and UCN2 were down-expressed in LC tissues as compared to their paired ANMMTs. The COL7A1:β-actin ratio in COL7A1-UCN2-positive LC samples was significantly lower than that in COL7A1-UCN2-negative samples (p = 0.019). Likewise, the UCN2:β-actin ratio was also decreased (p = 0.21). Furthermore, COL7A1-UCN2 positivity was significantly associated with the overall survival of LC patients (p = 0.032; HR, 13.2 [95%CI, 1.2–149.5]).ConclusionLC cells were enriched in the recurrent chimera COL7A1-UCN2, which potentially affected cancer stem cell transition, promoted epithelial-mesenchymal transition in LC, and resulted in poorer prognoses.

Highlights

As hybrid RNAs, transcription-induced chimeras (TICs) may have tumor-promoting properties, and some specific chimeras have become important diagnostic markers and therapeutic targets for cancer
In comprehensively analyzing novel TICs in transcriptomes in laryngeal cancer (LC) cells using a paired-end strategy for RNA deep sequencing, we found that COL7A1-urocortin 2 (UCN2) is a novel TIC
Transcriptome sequences in human LC and Adjacent normal mucous membrane tissue (ANMMT) samples We compared the transcriptome sequences in LC and paired normal tissue samples and identified a series of gene fusions and differentially expressed genes

Summary

Introduction

As hybrid RNAs, transcription-induced chimeras (TICs) may have tumor-promoting properties, and some specific chimeras have become important diagnostic markers and therapeutic targets for cancer. Like other carcinomas of the respiratory system, carcinogen exposure via tobacco smoke causes DNA damage, and the accumulation of this DNA damage can alter genetic and epigenetic regulatory functions and thereby transform normal cells into cancer cells [2, 3]. This cell transformation usually takes multiple steps to complete, and it is affected by the sensitivity of the individual and the degree of damage [4]. Some specific gene fusions have become important diagnostic markers of and therapeutic targets in cancer over the past several decades [7]. Other fusion genes, including PRCCTFE3 in papillary renal cell carcinoma [10], PAX8-PPARG in follicular thyroid carcinoma [11], FUS-CREB3L2 in soft

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