Abstract.Fascin is an actin cross-linking protein, which regulates actin dynamics and filopodia or spike formation, as well as the epithelial-mesenchymal transition, and has been implicated in cell motility. Although, fascin is pivotal in mediating the aggressive behaviour of various types of cancer, its prognostic significance according to tumour stage has yet to be evaluated. Therefore, the present study investigated fascin expression in 194 patients diagnosed with invasive ductal carcinoma of the breast between 2000 and 2005. Fascin protein expression levels were evaluated by immunostaining on a tissue microarray, and the association between fascin expression and various clinicopathological parameters was analysed. Fascin expression was significantly correlated with various clinicopathological parameters, including high histological grade, tumour necrosis, resistance to adjuvant therapy, high expression of p53 and Ki-67 and specific therapeutic markers (oestrogen and progesterone receptor negativity; all P<0.05). Furthermore, univariate and multivariate analyses identified a significant association between fascin expression, and poor disease-free and overall survival, in late-stage breast cancer (all P<0.05). Therefore, fascin may be crucial in predicting aggressive tumour behaviour, particularly in patients with advanced-stage disease that has acquired the properties of migration and invasion. IntroductionBreast cancer is the most commonly diagnosed neoplasm and the third leading cause of cancer-associated mortality in the United States, with 22.2 mortalities per 100,000 women associated with breast cancer each year. The five-year relative survival rate for breast cancer has gradually increased since the early 1990s and between 2007 and 2011 it was ~89.2%. However, the prognosis of patients with breast cancer is dependent on the disease stage at the time of diagnosis. In particular, the survival rates of patients with localised disease and regional lymph node metastasis at diagnosis are higher than those of patients presenting with distant metastasis (1). A number of studies have established molecular markers, which are associated with distinct histopathological features, the response to adjuvant therapy and/or the clinical outcome of breast cancer (2-7). Furthermore, the following clinicopathological factors are considered to be useful markers for predicting prognosis and identifying therapeutic targets in patients with advanced breast cancer: American Joint Committee on Cancer (AJCC) stage, histological grade, oestrogen receptor (ER) and progesterone receptor (PR) expression, human epithelial growth factor receptor 2 (HER2) amplification, p53 expression and Ki-67 labelling index (2-6). Based on data obtained from molecular or immunohistochemical (IHC) analyses, breast cancer is classified into four major subtypes: Luminal A, luminal B, basal-like and HER2-positive (7). More recently, the luminal B subtype has been subdivided according to HER2 status and Ki-67 labelling index (8).Despite improvements in the...

Gamma‐butyrobetaine dioxygenase (BBOX1) is a catalyst for the conversion of gamma‐butyrobetaine to l‐carnitine, which is detected in normal renal tubules. The purpose of this study was to analyze the prognosis, immune response, and genetic alterations associated with low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). We analyzed the relative influence of BBOX1 on survival using machine learning and investigated drugs that can inhibit renal cancer cells with low BBOX1 expression. We analyzed clinicopathologic factors, survival rates, immune profiles, and gene sets according to BBOX1 expression in a total of 857 patients with kidney cancer from the Hanyang University Hospital cohort (247 cases) and The Cancer Genome Atlas (610 cases). We employed immunohistochemical staining, gene set enrichment analysis, in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machines. BBOX1 expression in RCC was decreased compared with that in normal tissues. Low BBOX1 expression was associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils. In gene set enrichment analyses, low BBOX1 expression was related to gene sets with oncogenic activity and a weak immune response. In pathway network analysis, BBOX1 was linked to regulation of various T cells and programmed death‐ligand 1. In vitro drug screening showed that midostaurin, BAY‐61‐3606, GSK690693, and linifanib inhibited the growth of RCC cells with low BBOX1 expression. Low BBOX1 expression in patients with RCC is related to short survival time and reduced CD8+ T cells; midostaurin, among other drugs, may have enhanced therapeutic effects in this context.

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