RESUMEN
To date, the epigenetic signature of preeclampsia (PE) is not completely deciphered. Oxidative stress-responsive long non-coding RNAs (lncRNAs) are deregulated in preeclamptic placenta; however, their circulating profiles and diagnostic abilities are still unexplored. We investigated serum redox-sensitive lncRNAs TUG1, H19, and NEAT1, and their target miR-29b/cystine/neutral/dibasic amino acids transporter solute carrier family 3, member 1 (SLC3A1) as potential non-invasive biomarkers of PE risk, onset, and severity. We recruited 82 patients with PE and 78 healthy pregnant women. We classified PE patients into early-onset (EOPE) and late-onset (LOPE) subgroups at a cut-off 34 gestational weeks and into severe and mild PE subgroups by blood pressure and proteinuria criteria. Bioinformatics analysis was employed to select lncRNAs/microRNA/target gene interactions. Serum H19, NEAT1, and SLC3A1 mRNA expression were reduced, meanwhile miR-29b levels were elevated, whereas there was no significant difference in TUG1 levels between PE patients and healthy pregnancies. Serum H19 levels were lower, whereas miR-29b levels were higher in EOPE versus LOPE. Serum miR-29b and H19 levels were higher in severe versus mild PE. ROC analysis identified serum H19, NEAT1, miR-29b, and SLC3A1 as potential diagnostic markers, with H19 (AUC = 0.818, 95%CI = 0.744-0.894) and miR-29b (AUC = 0.82, 95%CI = 0.755-0.885) were superior discriminators. Only H19 and miR-29b discriminated EOPE and severe PE cases. In multivariate logistic analysis, miR-29b and H19 were associated with EOPE, using maternal age and gestational age as covariates, while miR-29b was associated with severe PE, using maternal age as covariate. Studied markers were correlated with clinical and ultrasound data in the overall PE group. Serum H19 and TUG1 were negatively correlated with albuminuria in EOPE and LOPE, respectively. NEAT1 and SLC3A1 were correlated with ultrasound data in EOPE. Likewise, TUG1, miR-29b, and SLC3A1 showed significant correlations with ultrasound data in LOPE. Conclusively, this study configures SLC3A1 expression as a novel potential serum biomarker of PE and advocates serum H19 and miR-29b as biomarkers of EOPE and miR-29b as a biomarker of PE severity.
RESUMEN
Background & Objective: Cervical cancer spreads to the pelvic lymph nodes, leading to a high incidence of cancer recurrence and unfavorable survival rates. Therefore, there is an urgent need to detect new predictive biomarkers for the early assessment of pelvic lymph node status in patients with cervical cancer. The current study aimed to assess the expression of FABP4, GINS2, and CBX7 in cervical cancer tissue to detect their prognostic and predictive roles in developing lymph node metastases in patients with that cancer type. Methods: We collected the tissues from patients with cervical cancer and evaluated the expression of FABP4, GINS2, and CBX7 using immunohistochemistry. We evaluated the association between their expression and clinicopathological and prognostic parameters. Results: A high expression of FABP4 and GINS2 and a low expression of CBX7 were found to be positively associated with the old age group, large tumor size, high grade and lymphovascular involvement, para-uterine organ infiltration, advanced FIGO stage, chemotherapeutic resistance, and tumor recurrence. Conclusion: We demonstrated the oncogenic roles of FABP4 and GISN2 in addition to the on-co-suppressive roles of CBX7 in cervical cancer and their association with poor clinicopathological criteria and poor survival. Our results may indicate that FABP4, GISN2, and CBX7 could be considered predictive biomarkers of the occurrence of lymph node metastases in the cancer of the cervix preoperatively, which could be beneficial in the accurate preoperative design therapy.