TY - JOUR
T1 - Identification of novel enriched recurrent chimeric COL7A1-UCN2 in human laryngeal cancer samples using deep sequencing
AU - Tao, Ye
AU - Gross, Neil
AU - Fan, Xiaojiao
AU - Yang, Jianming
AU - Teng, Maikun
AU - Li, Xu
AU - Li, Guojun
AU - Zhang, Yang
AU - Huang, Zhigang
N1 - Funding Information:
This work was supported by China National Science Foundation (Grant N0.81670946), which supported the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/3/2
Y1 - 2018/3/2
N2 - Background: 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. Methods: We 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. Results: We 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]). Conclusion: LC 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.
AB - Background: 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. Methods: We 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. Results: We 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]). Conclusion: LC 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.
KW - COL7A1
KW - Gene fusion
KW - Laryngeal cancer
KW - Transcription-induced chimera
KW - UCN2
UR - http://www.scopus.com/inward/record.url?scp=85042884582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042884582&partnerID=8YFLogxK
U2 - 10.1186/s12885-018-4161-8
DO - 10.1186/s12885-018-4161-8
M3 - Article
C2 - 29499655
AN - SCOPUS:85042884582
SN - 1471-2407
VL - 18
JO - BMC cancer
JF - BMC cancer
IS - 1
M1 - 248
ER -