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Open AccessArticle

Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data

1
College of Automation, Harbin Engineering University, Harbin 150001, China
2
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
3
The Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University, Indianapolis, IN 46202, USA
*
Authors to whom correspondence should be addressed.
Equal contributors.
Genes 2019, 10(10), 753; https://doi.org/10.3390/genes10100753
Received: 3 July 2019 / Revised: 19 September 2019 / Accepted: 20 September 2019 / Published: 25 September 2019
Alternatively-activated pathways have been observed in biological experiments in cancer studies, but the concept had not been fully explored in computational cancer system biology. Therefore, an alternatively-activated pathway identification method was proposed and applied to primary breast cancer and breast cancer liver metastasis research using microarray data. Interestingly, the results show that cytokine-cytokine receptor interaction and calcium signaling were significantly enriched under both conditions. TGF beta signaling was found to be the hub in network topology analysis. In total, three types of alternatively-activated pathways were recognized. In the cytokine-cytokine receptor interaction pathway, four active alteration patterns in gene pairs were noticed. Thirteen cytokine-cytokine receptor pairs with inverse activity changes of both genes were verified by the literature. The second type was that some sub-pathways were active under only one condition. For the third type, nodes were significantly active in both conditions, but with different active genes. In the calcium signaling and TGF beta signaling pathways, node E2F5 and E2F4 were significantly active in primary breast cancer and metastasis, respectively. Overall, our study demonstrated the first time using microarray data to identify alternatively-activated pathways in breast cancer liver metastasis. The results showed that the proposed method was valid and effective, which could be helpful for future research for understanding the mechanism of breast cancer metastasis. View Full-Text
Keywords: alternatively-activated pathway; breast cancer; liver metastasis; microarray; gene active status alternatively-activated pathway; breast cancer; liver metastasis; microarray; gene active status
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Wang, L.; Li, J.; Liu, E.; Kinnebrew, G.; Zhang, X.; Stover, D.; Huo, Y.; Zeng, Z.; Jiang, W.; Cheng, L.; Feng, W.; Li, L. Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data. Genes 2019, 10, 753.

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