RESUMEN
Purpose: To investigate the association between subtypes of metabolic syndrome (MetS) and prognosis of patients with stage I endometrioid adenocarcinoma. Patients and methods: Patients with stage I endometrioid adenocarcinoma who received surgical treatment as primary therapy at the Department of Gynecology of the Sun Yat-sen Memorial Hospital between June 2015 and December 2019 were retrospectively enrolled. According to the diagnosis criteria of MetS, the patients were categorized as patients without MetS, patients with MetS but without raised fasting plasma glucose (FPG, including previously diagnosed diabetes), and patients with MetS and raised FPG. All the included patients were followed from the dates of surgery until death, June 2021, or loss to follow-up, whichever came first, and cancer recurrence (including metastasis) was studied as the main outcome. Cox regression was used to evaluate the associations between subtypes of MetS and the study outcome adjusting for potential confounding factors. Results: Among the included 387 patients with stage I endometrioid adenocarcinoma, 193 (49.9%) were without MetS, 65 (16.8%) were with FPG not involving MetS, and 129 (33.3%) were with raised FPG involved MetS. With a median follow-up of 1,253 days, the cumulative incidence of cancer recurrence was 8.76% (95% confidence interval (CI) 2.5%-14.62%), 28.31% (95% CI 2.33%-47.38%), and 7.54% (95% CI 1.54%-13.17%), respectively. After adjusting for age, menopause, histological grade, tumor size, lymph-vascular space invasion, deep myometrial invasion, and treatments, comorbid FPG not involving MetS is a stronger risk factor of cancer recurrence than comorbid raised FPG involving MetS (hazard ratio 2.82 (95% CI 1.10-7.24) versus 1.18 (95% CI 0.45-3.13)) when compared to patients without MetS. Conclusion: Comorbid MetS generally presents as a risk factor of poor prognosis in patients with stage I endometrioid adenocarcinoma after surgical treatment, but the magnitude of the association may vary between subtypes, in which FPG not involving MetS appears to be predominant.
RESUMEN
BACKGROUND: The multiple causes of oligohydramnios make it challenging to study. Long noncoding RNAs (lncRNAs) are sets of RNAs that have been proven to function in multiple biological processes. The purpose of this study is to study expression level and possible role of lncRNAs in oligohydramnios. METHODS: In this study, total RNA was isolated from fetal membranes resected from oligohydramnios pregnant women (OP) and normal amount of amniotic fluid pregnant women (Normal). LncRNA microarray was used to analyze the differentially expressed lncRNAs and mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to analyze the main enrichment pathways of differentially expressed mRNAs. Real-time quantitative PCR (qPCR) was used to validate the lncRNA expression level. RESULTS: LncRNA microarray analysis revealed that a total of 801 lncRNAs and 367 mRNAs were differentially expressed in OP; in these results, 638 lncRNAs and 189 mRNAs were upregulated, and 163 lncRNAs and 178 mRNAs were downregulated. Of the lncRNAs, 566 were intergenic lncRNAs, 351 were intronic antisense lncRNAs, and 300 were natural antisense lncRNAs. The differentially expressed lncRNAs were primarily located in chromosomes 2, 1, and 11. KEGG enrichment pathways revealed that the differentially expressed mRNAs were enriched in focal adhesion as well as in the signaling pathways of Ras, tumor necrosis factor (TNF), estrogen, and chemokine. The qPCR results confirmed that LINC00515 and RP11-388P9.2 were upregulated in OP. Furthermore, the constructed lncRNA-miRNA-mRNA regulatory network revealed tenascin R (TNR), cystic fibrosis transmembrane conductance regulator (CFTR), ATP-binding cassette sub-family A member 12 (ABCA12), and collagen 9A2 (COL9A2) as the candidate targets of LINC00515 and RP11-388P9.2. CONCLUSIONS: In summary, we revealed the profiles of lncRNA and mRNA in OP. These results might offer potential targets for biological prevention for pregnant women with oligohydramnios detected before delivery and provided a reliable basis for clinical biological treatment in OP.
Asunto(s)
Membranas Extraembrionarias/metabolismo , Regulación de la Expresión Génica , Marcadores Genéticos , Oligohidramnios/diagnóstico , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , Transcriptoma , Adulto , Estudios de Casos y Controles , Biología Computacional , Femenino , Humanos , Masculino , Oligohidramnios/sangre , Oligohidramnios/genética , Embarazo , Análisis de Secuencia de ARNRESUMEN
The CreERT2 recombinase system is an advanced method to temporally control site-specific mutagenesis in adult rodents. In this process, tamoxifen is injected to induce Cre recombinase expression, and then, Cre recombinase can excise LoxP-flanked DNA. However, tamoxifen is a nonselective estrogen receptor antagonist that may influence behavioral alterations. Therefore, we designed five different protocols (acute effects, chronic effects, chronic effects after social defeat model, chronic effects after learned helplessness model, chronic effects after isolation models) to explore whether tamoxifen affects mouse behavior. Researching the acute/chronic effects of tamoxifen, we found that tamoxifen could influence locomotor activity, anxiety and immobility time in the forced swimming test. Researching the chronic effects of tamoxifen after social defeat/learned helplessness/isolation models, we found that tamoxifen could also influence locomotor activity, social interaction and anxiety. Therefore, the effects of tamoxifen are more complex than previously reported. Our results show, for the first time, that tamoxifen affects behavior in mouse models. Meanwhile, we compare the effects of tamoxifen in different protocols. These results will provide important information when designing similar experiments.