SGK1 regulated apoptosis in invasive breast carcinoma.

Abstract

e13061 Background: Worldwide, breast cancer is the most common type of cancers and the presentation of drug resistance is often associated with poor prognosis. Previous studies have shown the mechanism of drug resistance was affected by apoptosis at different levels in the signaling cascades. This article is aimed to explore the relationship between the serum and glucocorticoid-regulated kinase 1 (SGK1) and apoptosis in invasive breast cancer (IBC). Methods: We evaluated the expression of SGK1 in IBC using publicly available data from The Cancer Genome Atlas (TCGA) and Curtis Breast program. TaqMan probe-based qRT-PCR assay and Western Blot analysis were performed to quantitatively detect the expression of SGK1 at RNA and protein levels in the IBC specimens. Clinicopathologic characteristics associated with overall survival were tested by Cox regression. Gene Set Enrichment Analysis (GSEA) was performed to mine the biological pathways involved in IBC pathogenesis related SGK1 regulatory network using MSigDB database. Immunohistochemistry staining (IHC) was used to detect apoptotic markers Fas, Bcl2 and SGK1 in the IBC specimens. Results: Totally 1109 IBC samples with SGK1 expression data were downloaded from TCGA databases for analyzed. SGK1 expression was elevated in normal breast tissues compared with both invasive ductal carcinoma and invasive lobular carcinoma (p < 0.0001). Among them, SKG expression in 112 tumor tissues was significantly lower than that in paracancerous tissues, especially in advanced patients with TNM stage IV. Western Blot and qRT-PCR assay confirmed that SGK1 expression in IBC was distinctly lower than normal. The Kaplan-Meier survival analysis showed that decreased expression of SGK1 was significantly correlated with the clinical stage (p = 0.036). In Curtis Breast program, we further verified SGK1 gene expression was reduced in stage IV than stage I. The univariate analysis demonstrated that clinicopathologic variables associated with poor survival include age, advanced stage, lymph nodes, distant metastasis and deep myometrial invasion. GSEA revealed that apoptosis was differentially enriched when SGK1 was highly expressed. Similarly, TCGA data indicated that the positive rate of SGK1 was higher in Fas positive IBCs, and the same result was also obtained by IHC in the IBC specimens. Conclusions: Expression of SGK1 regulated apoptosis in invasive breast carcinoma, which might be a potential therapeutic target to overcome refractory and drug-resistant breast cancer.