Integrative analysis of multi-omics data reveals distinct impacts of DDB1-CUL4 associated factors in human lung adenocarcinomas

Journal Article · Thu Mar 23 00:00:00 EDT 2017 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-017-00512-1· OSTI ID:1408492

Yan, Hong ^[1]; Bi, Lei ^[2]; Wang, Yunshan ^[3]; Zhang, Xia ^[4]; Hou, Zhibo ^[5]; Wang, Qian ^[6]; Snijders, Antoine M. ^[7]; Mao, Jian-Hua ^[7]

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1. Nanjing Chest Hospital, Nanjing (China). Dept. of Lab. Medicine; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Nanjing University of Chinese Medicine, Nanjing (China). School of Preclinical Medicine
3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Shandong Univ. School of Ocean, Weihai, Shandong (China). International Biotechnology R&D Center
4. Nanjing Chest Hospital, Nanjing (China). Dept. of Tuberculosis
5. Nanjing Chest Hospital, Nanjing (China). Dept. of First Respiratory
6. Nanjing Chest Hospital, Nanjing (China). Dept. of Lab. Medicine
7. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division

Many DDB1-CUL4 associated factors (DCAFs) have been identified and serve as substrate receptors. Although the oncogenic role of CUL4A has been well established, specific DCAFs involved in cancer development remain largely unknown. Here we infer the potential impact of 19 well-defined DCAFs in human lung adenocarcinomas (LuADCs) using integrative omics analyses, and discover that mRNA levels of DTL, DCAF4, 12 and 13 are consistently elevated whereas VBRBP is reduced in LuADCs compared to normal lung tissues. The transcriptional levels of DCAFs are significantly correlated with their gene copy number variations. SKIP2, DTL, DCAF6, 7, 8, 13 and 17 are frequently gained whereas VPRBP, PHIP, DCAF10, 12 and 15 are frequently lost. We find that only transcriptional level of DTL is robustly, significantly and negatively correlated with overall survival across independent datasets. Moreover, DTL-correlated genes are enriched in cell cycle and DNA repair pathways. We also identified that the levels of 25 proteins were significantly associated with DTL overexpression in LuADCs, which include significant decreases in protein level of the tumor supressor genes such as PDCD4, NKX2-1 and PRKAA1. In conclusion, our results suggest that different CUL4-DCAF axis plays the distinct roles in LuADC development with possible relevance for therapeutic target development.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Natural Science Foundation of China (NSFC)
• Grant/Contract Number: AC02-05CH11231; R01 CA116481; 81273638; 81503486; 81402193; 81500029
• OSTI ID: 1408492
• Journal Information: Scientific Reports, Vol. 7, Issue 1; ISSN 2045-2322
• Publisher: Nature Publishing Group
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES