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Having markers feasible for breast cancer subtyping, especially for triple negative breast cancer identification is crucial for improving the treatment outcome of such cancers. Here we explore the role of FOXA1 in characterizing triple negative breast cancers and the driving mechanisms. Through in vitro examination of the expression pattern at both transcriptional and translational levels, patient relapse-free survival analysis, immunohistochemistry staining and prediction power assessment using clinical samples, as well as functional studies, we systematically compared the role of FOXA1 in identifying triple negative and luminal type of breast cancers and explored the mechanisms driving such functionalities. We report that FOXA1 under-expression can lead to increased malignancy and cancer stemness, and is a subtyping marker identifying triple negative breast cancers rather than the luminal subtype by transcriptionally suppressing the expression of SOD2 and IL6 . We are the first to systematically address the significance of FOXA1 in triple negative breast cancer identification as a biomarker and elucidate the mechanism at the molecular level, through a sequential bioinformatics analysis and experimental validations both in vitro and in clinics. Our discoveries compliment the current biomarker modalities once verified using larger clinical cohorts and improve the precision on characterizing breast cancer heterogeneity.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. However, to date, there is no ideal therapy for this disease. AIM To study the effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice. METHODS Twenty-four male C57BL/6 mice were randomized into three groups of eight. The control group (CON) was allowed ad libitum access to a normal chow diet. The high fat diet group (FAT) and Si-Ni-San group (SNS) were allowed ad libitum access to a high fat diet. The SNS group was intragastrically administered Si-Ni-San freeze-dried powder (5.0 g/kg) once daily, and the CON and FAT groups were intragastrically administered distilled water. After 12 wk, body weight, liver index, visceral fat index, serum alanine aminotransferase (ALT), portal lipopoly-saccharide (LPS), liver tumor necrosis factor (TNF)-α and liver triglycerides were measured. Intestinal microbiota were analyzed using a 16S r DNA sequencing technique. RESULTS Compared with the FAT group, the SNS group exhibited decreased body weight, liver index, visceral fat index, serum ALT, portal LPS, liver TNF-α and liver triglycerides ( P < 0.05). Intestinal microbiota analysis showed that the SNS group had different bacterial composition and function compared with the FAT group. In particular, Oscillospira genus was a bacterial biomarker of SNS group samples. CONCLUSION The beneficial effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice may be associated with its anti-inflammatory and changing intestinal microbiota effects.

BackgroundThe role of matrix metalloproteinase 9 (MMP-9) polymorphisms in breast cancer risk remains unclear. The purpose of this study was to evaluate the association between MMP-9 variants and breast cancer susceptibility.Material/MethodsCase-control studies were searched on electronic databases to retrieve related articles published between 2000 and 2014 concerning the role of MMP-9 variants in breast cancer risk. Pooled odds ratios (OR) with correlative 95% confidence intervals (CI) were employed to assess this association.ResultsTen articles were screened out, including 6177 breast cancer patients and 6726 matched-controls. For rs3918242 (−1562 C/T), 6 studies contained 1435 patients and 1446 controls. Although the frequency of risk allele C was higher in breast cancer patients than in controls, only TT genotype in recessive model was significantly associated with increased risk of breast cancer (TT vs. CT+CC: OR=1.55, 95% CI=1.12–2.16, P=0.009) in a fixed-effects model. This significant relationship was not observed in other genetic models (P>0.05). No significant association was found between breast cancer risk and rs17576, rs2250889, and rs3787268 under any genetic models.ConclusionsOur results show that TT genotype of MMP-9–1562 C/T polymorphism might be a risk factor for breast cancer. More studies are needed to further explore this association.

This meta-analysis suggests that statins have favorable effects on gastric cancer, rigorously designed and executed observational studies and randomized control trials with longer duration of follow-up are warranted to determine effects in clinical practice.