k-core genes underpin structural features of breast cancer

Abstract

Gene co-expression networks (GCNs) have been developed as relevant analytical tools for the study of the gene expression patterns behind complex phenotypes. Determining the association between structure and function in GCNs is a current challenge in biomedical research. Several structural differences between GCNs of breast cancer and healthy phenotypes have been reported. In a previous study, using co-expression multilayer networks, we have shown that there are abrupt differences in the connectivity patterns of the GCN of basal-like breast cancer between top co-expressed gene-pairs and the remaining gene-pairs. Here, we compared the top-100,000 interactions networks for the four breast cancer phenotypes (Luminal-A, Luminal-B, Her2+ and Basal), in terms of structural properties. For this purpose, we used the graph-theoretical k-core of a network (maximal sub-network with nodes of degree at least k). We developed a comprehensive analysis of the network k-core ($$k=30$$ k = 30 ) structures in cancer, and its relationship with biological functions. We found that in the Top-100,000-edges networks, the majority of interactions in breast cancer networks are intra-chromosome, meanwhile inter-chromosome interactions serve as connecting bridges between clusters. Moreover, core genes in the healthy network are strongly associated with processes such as metabolism and cell cycle. In breast cancer, only the core of Luminal A is related to those processes, and genes in its core are over-expressed. The intersection of the core nodes in all subtypes of cancer is composed only by genes in the chr8q24.3 region. This region has been observed to be highly amplified in several cancers before, and its appearance in the intersection of the four breast cancer k-cores, may suggest that local co-expression is a conserved phenomenon in cancer. Considering the many intricacies associated with these phenomena and the vast amount of research in epigenomic regulation which is currently undergoing, there is a need for further research on the epigenomic effects on the structure and function of gene co-expression networks in cancer.

Gene Co-Expression in Breast Cancer: A Matter of Distance

“…The effect of loss in long range co-expression is consistent with previous works of regulatory networks in breast cancer ( 10 , 12 – 14 , 33 , 53 ). The block-type structure of the basal subtype matrix suggests the utility of clustering analysis to compare the structural properties of the correlation matrices.…”

“…In cancer, gene co-expression networks have been used to uncover genes and relationships that may represent crucial elements to determine differences between phenotypes ( 32 ). In particular, in breast cancer and breast cancer molecular subtypes ( 4 ), gene co-expression networks have been useful to identify the phenomenon of loss of long-range co-expression ( 10 , 12 , 14 , 33 ): this is, a property observed in cancer networks in which the most significant gene co-expression relationships occur between genes that belong to the same chromosome, i.e., cis- interactions. Conversely, inter-chromosome ( trans- ) interactions are often weak in cancer.…”

Oncogenic Role of miR-217 During Clear Cell Renal Carcinoma Progression

“…The bias to intra-chromosomal interactions has been previously reported by our group in gene co-expression networks for breast cancer (28,48,(70)(71)(72), lung cancer (31), and also CCRC (32). These results show a clear trend to favor close gene correlations in terms of base pair distance.…”

MATTE: anti-noise module alignment for phenotype-gene-related analysis

“…Regarding the enrichment of a chromosome location, chr16p13 is exceptionally significant. Many studies have confirmed that mutations and abnormal expression of the region are highly correlated with breast cancer [22][23][24] . The result of gene enrich in gene ontology(GO) shows the microtubule cytoskeleton involved in mitosis is highly correlated with the development of TNBC, which is highly consistent with the clinical practice and some research 25,26 .…”