Integrated diagnostic network construction reveals a 4-gene panel and 5 cancer hallmarks driving breast cancer heterogeneity

Abstract

Breast cancer encompasses a group of heterogeneous diseases, each associated with distinct clinical implications. Dozens of molecular biomarkers capable of categorizing tumors into clinically relevant subgroups have been proposed which, though considerably contribute in precision medicine, complicate our understandings toward breast cancer subtyping and its clinical translation. To decipher the networking of markers with diagnostic roles on breast carcinomas, we constructed the diagnostic networks by incorporating 6 publically available gene expression datasets with protein interaction data retrieved from BioGRID on previously identified 1015 genes with breast cancer subtyping roles. The Greedy algorithm and mutual information were used to construct the integrated diagnostic network, resulting in 37 genes enclosing 43 interactions. Four genes, FAM134B, KIF2C, ALCAM, KIF1A, were identified having comparable subtyping efficacies with the initial 1015 genes evaluated by hierarchical clustering and cross validations that deploy support vector machine and k nearest neighbor algorithms. Pathway, Gene Ontology, and proliferation marker enrichment analyses collectively suggest 5 primary cancer hallmarks driving breast cancer differentiation, with those contributing to uncontrolled proliferation being the most prominent. Our results propose a 37-gene integrated diagnostic network implicating 5 cancer hallmarks that drives breast cancer heterogeneity and, in particular, a 4-gene panel with clinical diagnostic translation potential.

FAM134B promotes esophageal squamous cell carcinoma in vitro and its correlations with clinicopathologic features

“…carcinoma [11,12,27,30,34]. On the contrary, in this study, we noted that overexpression of [11,12].…”

“…Initial studies revealed that FAM134B acts as a transforming gene in ESCC and is overexpressed in ESCC cells [9]. Subsequent studies noted that FAM134B acts as a tumor suppressor and inhibits cancer growth in colorectal adenocarcinoma and breast carcinoma [11][12][13][14][15].…”

Role of undifferentiation markers and androgen receptor expression in triple‐negative breast cancer

“…ALCAM‐negative was described in 22% in a series with 2197 unselected BC patients, and similar rates were confirmed in smaller series. Based on the function of ALCAM as a cell adhesion molecule, it appears possible that loss of such a protein would result in more adverse cancer cell behavior due to a facilitated tissue infiltration for developing metastases and different series described its association with higher rates of recurrences, shorter survival, advanced stages, unfavorable tumor grade, and high Ki67 . However, we did not find the association between membrane ALCAM expression and survival in our series, nor its association with higher stage or higher Ki67.…”

“…Its expression in breast cancer (BC) is associated with aggressive clinicopathological features. Dai et al found that ALCAM is a negative prognosis marker, and its combination with other three genes related to cancer hallmarks is equivalent to previously identified 1015 genes for BC subtyping and has a remarkable role in distinguishing TNBC subtype …”

“…Dai et al found that ALCAM is a negative prognosis marker, and its combination with other three genes related to cancer hallmarks is equivalent to previously identified 1015 genes for BC subtyping and has a remarkable role in distinguishing TNBC subtype. 3 The insulin-like growth factor 2 messenger RNA-binding protein Histology was ductal in 96.84%, and median survival was 4.1 years. sTIL > 50% had a trend to predict survival (P = 0.07), and median CD8 was 10% and was associated with longer survival (P = 0.02; Figure 1).…”