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Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Research

Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study

Authors: Erfei Chen, Fangfang Yang, Hongjuan He, Qiqi Li, Wei Zhang, Jinliang Xing, Ziqing Zhu, Jingjing Jiang, Hua Wang, Xiaojuan Zhao, Ruitao Liu, Lei Lei, Jing Dong, Yuchen Pei, Ying Yang, Junqiang Pan, Pan Zhang, Shuzhen Liu, Le Du, Yuan Zeng, Jin Yang

Published in: Molecular Cancer | Issue 1/2018

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Abstract

Background

Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC.

Methods

We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study.

Results

We identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1.

Conclusions

Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.
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Metadata
Title
Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study
Authors
Erfei Chen
Fangfang Yang
Hongjuan He
Qiqi Li
Wei Zhang
Jinliang Xing
Ziqing Zhu
Jingjing Jiang
Hua Wang
Xiaojuan Zhao
Ruitao Liu
Lei Lei
Jing Dong
Yuchen Pei
Ying Yang
Junqiang Pan
Pan Zhang
Shuzhen Liu
Le Du
Yuan Zeng
Jin Yang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0925-7

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