Abstract
Dysregulation of Hedgehog (Hh) signaling pathway has been documented in mammary gland development and breast cancer (BC) progression. Despite the remarkable progress in therapeutic interventions, BC related mortality in Bangladesh increased in the last decade. Triple negative breast cancer (TNBC) still presents a critical therapeutic challenge. Thus effective targeted therapy is urgently needed. In this study, we report the clinicopathological characteristics and prognosis of BC patients from Bangladesh. Routine immunohistochemical analysis and high throughput RNA-Seq data from the TCGA library were used to analyze the expression pattern and association of high and low level of Shh expression in a collection of BC patients with a long-term follow-up. High levels of Shh were observed in a subset of BC tumors with poor prognostic pathological features. Higher level of Shh expression correlated with a significantly poorer overall survival of patients compared with patients whose tumors expressed a low level of Shh. These data support the contention that Shh could be a novel biomarker for breast cancer that is involved in mediating the aggressive phenotype of BC. We propose that BC patients exhibiting a higher level of Shh expression, representing a subset of BC patients, would be amenable to Shh targeted therapy.
Highlights
Gene expression analysis identified several molecular subtypes of breast cancer that are biologically and clinically distinct[3]
For patient #1, representing a sample of an nTNBC, Western blot results showed a moderate level of Shh expression in nTNBC, compared with a significant increased in a triple-negative breast cancer (TNBC) sample
Breast cancer (BC) is considered to constitute a heterogeneous group of tumors showing different behaviors, prognosis and response to treatment
Summary
Gene expression analysis identified several molecular subtypes of breast cancer that are biologically and clinically distinct[3]. One of these subtypes is triple-negative breast cancer (TNBC), which is negative in estrogen receptor (ER) and progesterone receptor (PR) and negative in human epidermal growth factor receptor 2 (HER2) overexpression[3]. A deeper understanding of the molecular pathways involved in breast cancer progression would lead to more effective targeted therapies to combat TNBC drug resistance and subsequent patient death. We report that Shh, a ligand of Hh signaling, is highly expressed in a significant fraction of human breast cancer patients exhibiting a significantly lower overall survival (OS) of the TNBC subtype
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