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

Abstract

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.

Rad21 is the core subunit of the cohesin complex involved in directing genome organization

“…S5d). Among the top 8 KEGG pathways, cytokine-cytokine receptor interaction, the TNF signaling pathway and the NOD-like receptor signaling pathway are known to play roles in breast cancer [36][37][38] . In addition, to obtain insight into the relationship between up-regulated Rad21 and breast cancer, we subjected breast cancer cell lines to gene set enrichment analysis (GSEA).…”

Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma

“…In support of our results, studies have demonstrated that E2F4 function as crucial regulator in liver cancer 38 . The increased E2F4 in breast cancer is also associated with breast cancer liver metastasis 39 . it is also estimated that E2F4 acts as bridging genes in the process of colorectal cancer liver metastasis 40 .…”

Identifies Immune-Related Gene Pair Signature Associated with Breast Cancer Prognosis

“…Among them, the cytokine-cytokine receptor pathway, as the top-ranked pathway, stimulated our interest. Previous researches have shown that cytokine-cytokine receptor interaction is significantly associated with many biological processes of BC, such as chemoresistance and metastasis of BC (26,27), which often leads to poor prognosis of patients with BC. In addition, MAPK signaling pathway (27), B cell receptor signaling pathway (28), and chemokine signaling pathway (29) are also important roles that affect the OS of patients with BC.…”