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Artigo em Inglês | MEDLINE | ID: mdl-33604715


PURPOSE: Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. METHODS: FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. RESULTS: Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS). CONCLUSIONS: This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.

J Trace Elem Med Biol ; 64: 126677, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33246299


OBJECTIVES: Selenium (Se) was a potential anticancer micronutrient with proposed epigenetic effect. However, the Se-induced epigenome in breast cancer cells was yet to be studied. METHODS: The profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) in breast cancer cells treated with sodium selenite were examined by microarrays. We verified the epigenetic modifications by integrating their predicted target genes and differentially expressed mRNAs. The epigenetically regulated genes were further validated in a breast cancer cohort by associating with tumor progression. We conducted a series of bioinformatics analyses to assess the biological function of these validated genes and identified the critical genes. RESULTS: The Se-induced epigenome regulated the expression of 959 genes, and 349 of them were further validated in the breast cancer cohort. Biological function analyses suggested that these validated genes were enriched in several cancer-related pathways, such as PI3K/Akt and metabolic pathways. Based on the degrees of expression change, hazard ratio difference, and connectivity, NEDD4L and FMO5 were identified as the critical genes. CONCLUSIONS: These results confirmed the epigenetic effects of sodium selenite and revealed the epigenetic profiles in breast cancer cells, which would help understand the mechanisms of Se against breast cancer.

Chemosphere ; 261: 128148, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33113665


Cadmium (Cd) has been confirmed to be associated with breast carcinogenesis, but the mechanism was not clarified yet. Given that epigenetic modification was speculated as underlying mechanism, we examined the differential epigenome caused by Cd in breast cancer cells. Profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) were derived from Cd-treated and untreated MCF-7 breast cancer cells by microarray. We identified 997 target genes epigenetically regulated by Cd through cross-verification with the differential epigenome and transcriptome, and 400 of them were further validated in a breast cancer cohort. Biological function analyses suggested that several pathways were involved in Cd-induced breast carcinogenesis, such as Wnt signaling, metabolism, and human papilloma virus (HPV) infection. TXNRD1 and CCT3 were further identified as the critical genes based on the degree of expression change, hazard ratio difference, and connectivity. The present study revealed that Cd epigenetically regulated several pathways involving in breast carcinogenesis, particularly the Wnt signaling and metabolic pathways, among which TXNRD1 and CCT3 might play critical roles. It was also suggested that Cd and HPV infection might jointly participate in breast tumorigenesis.

Neoplasias da Mama/genética , Cádmio/toxicidade , Carcinogênese/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Epigênese Genética/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Carcinogênese/genética , Metilação de DNA/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Análise Serial de Tecidos
Cancer Med ; 9(1): 385-393, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31724329


Reproductive factors associated with breast cancer risk may also affect the prognosis. This study aimed to evaluate the associations of multiple reproductive factors with breast cancer prognosis and the modifying effects of menopausal status. We obtained data from 3805 breast cancer patients recruited between October 2008 and June 2016 in Guangzhou. The subjects were followed up until 30 June 2018. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using multivariate Cox models to estimate the associations. It was found that there were U-shaped patterns for the associations of age at first birth and durations from first/last birth to diagnosis with breast cancer prognosis. The adverse effects of old age at first birth [>30 years vs 23-30 years, HR (95% CI): 1.59 (1.01-2.50)] and long intervals from first [≥20 years vs 10-19 years, HR (95% CI): 1.55 (1.07-2.27)] or last [≥20 years vs 10-19 years, HR (95% CI): 1.63 (1.08-2.46)] birth to diagnosis on progression-free survival (PFS) were significantly more pronounced among premenopausal women. Additionally, long interval (>5 years) between first and second birth was associated with a better PFS [HR (95% CI): 0.64 (0.42-0.97)]. These results suggested that age at first birth, durations from first/last birth to diagnosis, and intervals between first and second birth should be taken into account when following the patients and assessing the prognosis of breast cancer, particularly for premenopausal patients. These findings would also have implications for further insight into the mechanisms of breast cancer development.

Sleep Med ; 54: 153-158, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30580187


OBJECTIVES: Sleep has been closely linked to breast cancer risk. However, the association between sleep and breast cancer prognosis remains unclear. The aim of this study was to evaluate the separate and joint effects of multiple sleep characteristics on breast cancer prognosis among Chinese women. METHODS: A total of 1580 breast cancer patients were recruited between October 2008 and December 2014 and followed up until December 31, 2017 in Guangzhou. Multivariate Cox models were conducted to estimate the hazard ratios (HR) and 95% confidence intervals (95%CI) for breast cancer prognosis in association with sleep characteristics. RESULTS: Long sleep duration at night (>9 h) (HR = 2.33, 95%CI: 1.01-5.42), poor sleep quality (HR = 3.08, 95%CI: 1.74-5.47), and impaired daytime function (HR = 2.49, 95%CI: 1.65-3.79) after diagnosis were associated with an increased risk of breast cancer progression. Both short sleep duration (<6 h) (HR = 2.00, 95%CI: 1.06-3.77, Pinteraction = 0.011) and long sleep duration (>9 h) (HR = 4.69, 95%CI: 1.31-16.78, Pinteraction = 0.187) increased the progression risk only among patients with impaired but not normal daytime function. In addition, daytime napping significantly modified the effect of short sleep duration on the progression (HR = 3.55, 0.59, 95%CI: 1.55-7.97, 0.23-1.53 for patients without and with daytime napping, respectively, Pinteraction = 0.005). Stratification results suggested that the associations were more evident among pre-menopausal patients, although no significant interaction was observed. CONCLUSION: Our findings suggested that inadequate sleep duration to feel one's best and poor sleep quality after diagnosis were associated with an increased risk of breast cancer progression, particularly for pre-menopausal women.

Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Progressão da Doença , Menopausa/fisiologia , Sono/fisiologia , Adulto , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo