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Pancreatic adenocarcinoma (PAAD), the most common subtype of pancreatic cancer, is a highly lethal disease. In this study, we integrated the expression profiles of splicing factors (SFs) of PAAD from RNA-sequencing data to provide a comprehensive view of the clinical significance of SFs. A prognostic index (PI) based on SFs was developed using the least absolute shrinkage and selection operator (LASSO) COX analysis. The PI exhibited excellent performance in predicting the status of overall survival of PAAD patients. We also used the percent spliced in (PSI) value obtained from SpliceSeq software to quantify different types of alternative splicing (AS). The prognostic value of AS events was explored using univariate COX and LASSO COX analyses; AS-based PIs were also proposed. The integration of prognosis-associated SFs and AS events suggested the potential regulatory mechanisms of splicing processes in PAAD. This study defined the markedly clinical significance of SFs and provided novel insight into their potential regulatory mechanisms.

Association rules analysis is an important subject in data mining. At present, association rules mining algorithms frequently generate a large number of association rules, but most of the algorithm evaluations make advances only from an aspect, which makes the users select difficultly. Therefore, the comprehensive evaluation of association rules has become highly necessary. A comprehensive evaluation system of association rules based on the AHP (Analytic Hierarchy Process) was presented, which can evaluate the association rules from multi-angle and multi-dimensional. Many evaluation results are integrated into the system, eventually presenting a unified comprehensive coefficient to users. Practical data make it clear that the comprehensive evaluation system is rational and superior.

Objective Although many studies have documented the tumor-promoting role of hepsin in several types of malignancies, little is known about its clinical and biological significance in breast cancer. Materials and Methods Hepsin expression was examined in 4 pairs of fresh breast tumor samples and corresponding nontumor breast tissues by Western blotting. Immunohistochemistry for hepsin was performed on an additional cohort of 215 archival breast cancer samples. The clinical significance of hepsin expression was analyzed. Knockdown of hepsin expression was performed in 2 breast cancer cell lines, MDA-MB-231 and HER18, with a high abundance of endogenous hepsin, and the effects of hepsin silencing on cell invasion and proliferation were evaluated. Results Hepsin was aberrantly overexpressed in breast cancer tissues relative to adjacent nontumor tissues. Its overexpression was significantly associated with tumor stage ( P = 0.037), lymph node metastasis ( P = 0.010), estrogen receptor positivity ( P = 0.019), and progesterone receptor positivity ( P < 0.0001) in patients with breast cancer. Down-regulation of hepsin expression by small interfering RNA (siRNA) significantly reduced cell proliferation and invasion in both the MDA-MB-231 and HER18 cells compared to nonspecific control small interference RNA. Conclusion Our data demonstrate that hepsin expression is frequently up-regulated in breast cancer tissues, which is associated with tumor growth and progression. Thus, inhibition of hepsin expression might be of therapeutic significance.

Fascin, an actin-cross-linking protein, is up-regulated in breast cancer and correlates with a more aggressive disease. This study was conducted to elucidate the effects of manipulating fascin in breast cancer cells on the metastasis-associated events, including proliferation, adhesion, invasion, epithelial–mesenchymal transition (EMT) and enrichment of a CD44+/CD24− subpopulation that show some stem/progenitor cell properties. Western blot analysis of a panel of breast cancer cell lines revealed high expression of fascin in MDA-MB-435 and MDA-MB-231 cells but revealed no or low expression in MDA-MB-453, Her-18 and T47D. Gain-of-function and loss-of-function studies in breast cancer cells demonstrated that forced expression of fascin promoted cell proliferation assessed by the MTT assay, decreased cellular adhesion to fibronectin and potentiated the invasive capacity in the Transwell chamber invasion assay. Conversely, down-regulation of fascin via small interfering RNA increased cell adhesion and facilitated cell proliferation and invasion. In addition, fascin participated in the EMT and modulated the proportion of the CD44+/CD24− subpopulation in breast cancer cells. In conclusion, our data highlight an important role for fascin in breast cancer progression in vitro through orchestrating a variety of cellular events associated with metastasis, and thus, targeting this gene might have therapeutic implications. Copyright © 2011 John Wiley & Sons, Ltd.

Purpose: Obesity has been recognized as a significant risk factor for postmenopausal breast cancer. The aim of this study is to investigate the prognostic significance of body mass index (BMI) in hormone receptor-positive, operable breast cancer. Methods: In this retrospective cohort study, 1,192 consecutive patients with curative resection of primary breast cancer were enrolled. Patients were assigned to two groups according to BMI: normal or underweight (BMI < 23.0 kg/m2) and overweight or obese (BMI ≥23.0 kg/m2). Associations among BMI and clinicopathological characteristics and prognosis of patients were assessed. Results: A high BMI was significantly (P < 0.01) correlated with age, nodal stage, ALNR, ER positivity, PR positivity and menopausal status at diagnosis. Univariate analysis revealed that BMI, pathologic T stage, nodal stage, axillary lymph node ratio (ALNR) and adjuvant radiotherapy history were significantly (P < 0.05) associated with disease-free survival and overall survival, irrespective of tumour hormone receptor status. Multivariate analysis revealed BMI as an independent prognostic factor in all cases and in hormone receptor-positive cases. Conclusion: A high BMI (≥23.0 kg/m^2) is independently associated with poor prognosis in hormone receptor-positive breast cancer.