Distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis

Abstract

The present study aims at a platform-independent confirmation of previously obtained cDNA microarray results on inflammatory breast cancer (IBC) using Affymetrix chips. Gene-expression data of 19 IBC and 40 non-IBC specimens were subjected to clustering and principal component analysis. The performance of a previously identified IBC signature was tested using clustering and gene set enrichment analysis. The presence of different cell-of-origin subtypes in IBC was investigated and confirmed using immunohistochemistry on a TMA. Differential gene expression was analysed using SAM and topGO was used to identify the fingerprints of a pro-metastatic-signalling pathway. IBC and non-IBC have distinct gene-expression profiles. The differences in gene expression between IBC and non-IBC are captured within an IBC signature, identified in a platform-independent manner. Part of the gene-expression differences between IBC and non-IBC are attributable to the differential presence of the cell-of-origin subtypes, since IBC primarily segregated into the basal-like or ErbB2-overexpressing group. Strikingly, IBC tumour samples more closely resemble the gene-expression profile of T1/T2 tumours than the gene-expression profile or T3/T4 tumours. We identified the insulin-like growth factor-signalling pathway, potentially contributing to the biology of IBC. Our previous results have been validated in a platform-independent manner. The distinct biological behaviour of IBC is reflected in a distinct gene-expression profile. The fact that IBC tumours are quickly arising tumours might explain the close resemblance of the IBC gene-expression profile to the expression profile of T1/T2 tumours.

Regulation of Inflammatory Breast Cancer Cell Invasion through Akt1/PKBα Phosphorylation of RhoC GTPase

“…The result of the global test was corrected for the cell-of-origin subtype classification, which we reported on in previous studies (27,29). The set of 84 genes can be further subdivided into 8 biologic processes.…”

“…Before analysis, RNA was extracted from 34 IBC samples and 48 nonstage matched nIBC samples using protocols described previously (26). The dataset represents the same samples as reported on in earlier studies (26,27). Clinicopathologic data are provided in Supplementary Table 1.…”

“…Raw array data are publicly available on Array Express (accession number E-MTAB-1006). Microarray data were background corrected, normalized, summarized and log 2 -tranformed using the GCRMA-algorithm (27). A total of 22,419 Probe sets with fluorescence intensities above log 2 (100) in at least 25% of the arrays were filtered in and were considered informative for further analysis.…”

“…1B, differences in the PI3K/Akt pathway are associated with the basal-like molecular breast cancer subtype (Global test, P ¼ 0.022). As the basal-like breast cancer subtype is frequently observed in IBC (27,29), we conducted a global test for the PI3K/Akt pathway genes, comparing IBC with nIBC, and correcting for the influence of the molecular breast cancer subtypes. After correction, the global test comparing IBC to nIBC turned out to be inconsequential, indicating that, in general, the differential PI3K/Akt regulation associated with molecular subtype is not IBC-specific.…”

MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer

“…The few published mRNA expression profiling studies to date have indicated that transcriptional heterogeneity exists in inflammatory breast cancer as extensively as in noninflammatory breast cancer, and that the established molecular subtypes such as luminal, HER2-positive, and basal-type can be identified in inflammatory breast cancer. [5][6][7][8][9][10][11][12][13][14][15][16] Although some of the studies have demonstrated differences in mRNA expression levels between inflammatory breast cancer and noninflammatory breast cancer samples, a specific inflammatory breast cancer signature cannot be deduced from these studies.…”