Abstract 1972: Identification of novel candidate driver genes of colorectal cancer on chromosome 7p
Authors: Kouyama Yuta , Ogawa Yushi , Masuda Takaaki , Yoshikawa Yukihiro , Noda Miwa , Wakiyama Hiroaki , Sato Kuniaki , Nambara Sho , Hu Qingjiang , Kidogami Shinya , Saito Tomoko , Sakimura Shotaro , Hayashi Naoki , Kuroda Yohsuke , Ito Shuhei , Eguchi Hidetoshi , Mimori Koshi 
Published: July 2017

Background

Colorectal cancer (CRC) is one of the most prevalent types of cancer. The high mortality rate of CRC is a serious problem. Hence it is urgently necessary to identify novel molecular target to improve the mortality rate. Amplification of chromosome 7p is frequent in CRC, and it has been considered to harbor driver genes that promote tumorigenesis or tumor progression by the gain of function. The aim of this study is to identify novel candidate driver genes on chromosome 7p and to clarify the clinical significance of their expression in CRC.

Material and Methods

1. We selected the candidate genes that satisfied the following criteria using CRC data from The Cancer Genome Atlas (TCGA). 1) The DNA copy number and mRNA expression is positively correlated with each other, 2) overexpressed in the tumor tissues compared to the normal tissues. 2. The mRNA expression of the candidate genes was measured in 108 surgically-resected CRC tissues and the paired normal tissues in our hospital by quantitative RT-PCR. The differences of mRNA expression between CRC tissues and normal tissues were analyzed by Mann Whitney U-test. 3. Survival analysis between high and low expression group of the candidate genes was performed by Kaplan-Meier method. Correlation between the mRNA expression of the candidate genes and the clinicopathological factors were analyzed by Fisher’s exact test. 4. We performed Gene Set Enrichment Analysis (GSEA) in CRC data from TCGA to clarify the correlation between the candidate genes and gene sets that are associated with tumorigenesis or tumor progression.

Results

DEAD Box Helicase56 (DDX56), ATP-dependent RNA helicases involved in several aspects of RNA metabolism including mRNA splicing and transport, transcription, translation and remodeling of ribonucleoprotein complexes, was satisfied with the criteria. The expression of DDX56 was significantly higher in CRC tissues than in normal colon tissues (p&lt;0.005), and it correlated with lymphatic invasion (p=0.02), and distant metastasis (p=0.03). The high DDX56 expression group had a significantly poorer prognosis than the low expression group (p=0.03). On multivariate analysis, high DDX56 expression was an independent prognostic factor affecting OS (p=0.013) with hazard ratios (95% CI) of 2.32 (1.20-4.48) among clinicopathological factors. GSEA showed that DDX56 expression was positively correlated with mitotic cell cycle progression and spliceosome.

Conclusions

We identified DDX56 as a promising driver gene of CRC on chromosome 7p. DDX56 expression was positively associated with lymphatic invasion and distant metastasis, and was an independent poor prognostic factor. Furthermore, DDX56 may be involved in tumor progression through stimulating cell-cycle. DDX56 could be a therapeutic target as well as a poor prognostic biomarker in CRC.

Note: This abstract was not presented at the meeting.

Citation Format: Yuta Kouyama, Yushi Ogawa, Takaaki Masuda, Yukihiro Yoshikawa, Miwa Noda, Hiroaki Wakiyama, Kuniaki Sato, Sho Nambara, Qingjiang Hu, Shinya Kidogami, Tomoko Saito, Shotaro Sakimura, Naoki Hayashi, Yohsuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori. Identification of novel candidate driver genes of colorectal cancer on chromosome 7p [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1972. doi:10.1158/1538-7445.AM2017-1972