FOXC2 as a prognostic marker and a potential molecular target in patients with human solid tumors.

Background: Forkhead Box Protein C2 (FOXC2) belongs to the Forkhead/Wing-helix family. The regulatory role of this transcription factor in physiological function and carcinogenic activity has been proven in subsequent investigations. However, there is still scarcity of evidence on the relationship between FOXC2 expression and prognosis in human solid tumors. We conducted this meta-analysis to evaluate the role of FOXC2 as a prognosis factor and a possible target marker in human solid tumors. Methods: PubMed, Web of Science, Embase, and the Cochrane library database were all searched methodically. Eligible publications on FOXC2 in human solid tumors were gathered and reviewed. The effect sizes were calculated using pooled hazard ratios (HRs) or odds ratios (ORs) with the corresponding 95% confidence interval (CI). Statistical analysis was conducted with Stata SE12.0. Results: This meta-analysis comprised 3,267 patients from 20 studies covering a variety of solid tumors. Increased FOXC2 expression was related to shorter overall survival (OS) (HR = 2.05, 95% CI: 1.73-2.42). High expression of FOXC2 is associated with lymph node metastases (OR = 3.33, 95% CI: 2.65-4.19), TNM stage (OR = 3.09, 95% CI: 2.00-4.78), and age (OR = 1.26, 95% CI: 1.06-1.50), according to the pooled ORs. However, no significant association was observed between the high expression of FOXC2 and sex, tumor size or tumor differentiation. Conclusion: Increased expression of FOXC2 is associated with unfavored OS, lymph node metastases, TNM stage, and age. FOXC2 is a promising prognostic marker and a novel target marker in human solid tumors.

Prognostic value of high FOXO3a expression in patients with solid tumors: A meta-analysis and systematic review.

BACKGROUND: FOXO3a (previously termed FKHRL1), plays an evolutionarily conserved role in the control of biological process, including DNA damage, apoptosis, and cell cycle regulation. However, the role of FOXO3a in tumors remains controversial. This meta-analysis was conducted to evaluate the prognostic value of FOXO3a expression in patients with solid tumors. METHODS: A systematic literature search of the PubMed, Web of Science, Embase, and Cochrane Library databases was performed. Eligible publications on FOXO3a and cancer prognosis were collected and screened according to the eligibility criteria. The combined odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were used to assess the prognostic value of FOXO3a. Stata 12.0 software was used for statistical analysis. RESULTS: A total of 4058 patients from 21 articles on a variety of solid tumors were included. Meta-analysis showed that the increased FOXO3a expression level was associated with longer overall survival (HR = 0.62; 95% CI: 0.46-0.85). The pooled ORs indicated high expression level of FOXO3a in tumors was significantly associated with lymph node metastasis (OR = 0.46; 95% CI: 0.30-0.71), TNM stage (OR = 0.37; 95% CI: 0.25-0.54), tumor differentiation (OR = 0.46; 95% CI: 0.26-0.80), distant metastasis (OR = 0.44; 95% CI: 0.32-0.61), and age (OR = 1.28; 95% CI: 1.08-1.51). However, we did not observe a significant correlation between the high expression of FOXO3a and sex or tumor size. CONCLUSIONS: The high expression level of FOXO3a was associated with better clinical outcomes in solid tumors. FOXO3a may therefore serve as a potential prognostic biomarker and a promising molecular target.

The high expression of CHD1L and its clinical significance in human solid tumors: A meta-analysis.

BACKGROUND: Chromodomain helicase DNA-binding protein 1-like (CHD1L) is an oncogene. It was cloned from 1q21 chromosome region of hepatocellular carcinoma in 1991. CHD1L is up-regulated in many kinds of cancers and is involved in the carcinogenesis and development of tumors. More and more studies have shown that over-expression of CHD1L is associated with poor prognosis of tumors. The purpose of this study was to evaluate the prognostic value of CHD1L in human solid tumors. METHODS: The key words in the database of PubMed, Web of Science, Embase, Cochrane library, and TCGA were searched for systematic literature retrieval. We collected relevant articles and data about CHD1L and prognosis of cancer and screened them according to the eligible criteria to evaluate the prognostic value of CHD1L in cancer patients. Then Stata SE12.0 software is used to analyze the data. RESULTS: In our meta-analysis, 2720 patients with a total of 15 articles involving multiple types of tumors showed that high expression levels of CHD1L were associated with shorter overall survival (OS) (hazard ratio  = 2.21, 95% confidence interval [CI]: (1.49-3.30)] and (hazard ratio  = 1.16, 95% CI: (1.01-1.32)] in the TCGA database, in addition, the pooled odds ratios (ORs) indicated high expression levels of CHD1L in tumors significantly are associated with TNM stage (OR = 1.61, 95% CI: 1.01-2.55, P < .05), tumor size (OR = 1.38, 95% CI: 1.07-1.78, P < .05), tumor differentiation (OR = 2.13, 95% CI: 1.43-3.16, P < .05), and distant metastasis (OR = 1.86, 95% CI: 1.45-2.39 P < .05). However, we did not observe a significant correlation between the high expression of CHD1L and age, gender. CONCLUSION: The high expression of CHD1L is associated with poor OS as well as related to tumor differentiation, tumor size, and distant metastasis, which can be served as a prognostic marker and a potential predictor of clinical pathology in human solid tumors.

Mendelian randomization analysis of the association between human blood cell traits and uterine polyps.

Human blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79-0.93, P = 1.06 × 10-4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77-0.91, P = 2.43 × 10-5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.

Changes in the intestinal microecology induced by bacillus subtilis inhibit the occurrence of ulcerative colitis and associated cancers: a study on the mechanisms.

This study aimed to explore how changes in intestinal floras caused by Bacillus subtilis (Bs) inhibited occurrence of ulcerative colitis (UC) and associated cancers. Bs was used as an intervention in an azoxymethane (AOM)/dextran sodium sulfate sodium (DSS) animal model. Stool specimens were analyzed for changes in intestinal floras. Disease activity index (DAI) scores, body mass indices, cancer counts, and other indices were calculated, while changes in the colon mucosa were observed. Compared with AOM/DSS group, carcinogenesis significantly reduced and intestinal inflammations and DAI score alleviated; diversity, evenness, and number of species of floras significantly increased; and relative abundances of Rikenellaceae and Lactobacillus increased when UC developed into cancers in the AOM/DSS + Bs group. Colon epitheliums in the mice were severely damaged in the AOM/DSS group, while mucosae were repaired in the AOM/DSS + Bs group. The mRNA expression levels of IL-6 and IL-17a were lower while those of IL-10 and TGF-ß1 were higher, and the expression level of Ki-67 decreased while that of caspase 3 increased in the AOM/DSS + Bs group. Bs intervention could alter the structure of intestinal floras, repair the mucosal barrier, adjust immunity, and reduce the incidence of cancer in the AOM/DSS animal model.

Maternal iron intake during pregnancy and birth outcomes: a cross-sectional study in Northwest China.

Previous studies have yielded conflicting results on the associations of maternal Fe intake with birth outcomes. This study aimed to investigate the associations between maternal Fe intake (total Fe from diet and supplements, dietary total Fe, haeme Fe, non-haeme Fe and Fe supplements use) and adverse birth outcomes in Shaanxi Province of Northwest China. In all, 7375 women were recruited using a stratified multistage random sampling method at 0-12 months (median 3; 10th-90th percentile 0-7) after delivery. Diets were collected by a validated FFQ and maternal characteristics were obtained via a standard questionnaire. The highest tertile of haeme Fe intake compared with the lowest tertile was negatively associated with low birth weight (LBW) (OR 0·68; 95 % CI 0·49, 0·94), small for gestational age (SGA) (OR 0·76; 95 % CI 0·62, 0·94) and birth defects (OR 0·55; 95 % CI 0·32, 0·89). Maternal haeme Fe intake was associated with a lower risk of intra-uterine growth retardation (IUGR) (medium tertile v. lowest tertile: OR 0·78; 95 % CI 0·61, 0·95; highest tertile v. lowest tertile: OR 0·76; 95 % CI 0·59, 0·93; P trend=0·045). The OR of LBW associated with Fe supplements use were as follows: during pregnancy: 0·72 (95 % CI 0·50, 0·95); in the second trimester: 0·67 (95 % CI 0·42, 0·98); in the third trimester: 0·47 (95 % CI 0·24, 0·93). We observed no associations of total Fe, dietary total Fe or non-haeme Fe intake with birth outcomes. The results suggest that maternal haeme Fe intake is associated with a reduced risk of LBW, SGA, IUGR and birth defects, and Fe supplements use during pregnancy reduces LBW risk.