Bazarsad S, et al. Yonsei Med J. 2018 Aug;59(6):717-726. https://doi.org/10.3349/ymj.2018.59.6.717

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive form of epithelial ovarian cancer and is characterized by high recurrence rates and poor clinical outcomes. In this study, we identify molecular signatures associated with recurrence by conducting integrative transcriptomic and proteomic analyses on paired primary and recurrent HGSOC tissues from 34 patients. RNA sequencing and proteomic profiling revealed 185 differentially expressed genes (DEGs) and 36 differentially expressed proteins (DEPs) linked to recurrence. Pathway enrichment and Ingenuity pathway analyses highlighted the involvement of immune cell trafficking, cell signaling, and MAPK pathway activation in recurrent tumors. A survival analysis identified seven DEGs that correlated significantly with recurrence-free survival; among them, IL7R, IRF8, and PTPRC were upregulated in recurrent tumors and associated with poor prognosis, and NSG1 was downregulated and linked to favorable outcomes. Immunohistochemistry validated the differential expression of these markers at the protein level. The proteomic analysis demonstrated that recurrent tumor-specific DEGs are functionally linked to MAPK signaling. Co-expression analyses revealed dynamic regulatory interactions between the DEGs and DEPs, suggesting context-dependent molecular shifts during recurrence. This integrative multi-omics approach reveals that key molecular alterations underlie HGSOC recurrence and identifies IL7R, IRF8, PTPRC, and NSG1 as potential prognostic biomarkers and therapeutic targets. Our findings provide a foundation for targeted strategies to improve outcomes for patients with recurrent HGSOC.

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity, and early prediction is critical for timely intervention. This study aimed to identify predictive biomarkers for PE through transcriptomic analysis of second-trimester amniotic fluid supernatant (AFS) collected prior to clinical symptom onset. AFS samples from women who later developed PE (n = 7) and matched controls (n = 7) underwent RNA sequencing to identify differentially expressed genes (DEGs). Candidate genes were validated by real-time PCR in HTR-8/SVneo cells exposed to fluid shear stress at 3, 10, and 20 dyn/cm² for 24 h, mimicking the hemodynamic environment of PE, and siRNA-mediated knockdown was used to assess effects on trophoblast migration and invasion. RNA sequencing revealed 19 DEGs, with 3 upregulated and 16 downregulated genes in the PE group. HOOK2 emerged as the most significantly upregulated gene. Four candidate genes, including HOOK2, CCDC160, CKB, and PARP15, were selected for further validation. HOOK2 mRNA expression significantly increased with higher shear stress levels, consistent with sequencing data. Knockdown of HOOK2 led to a significant increase in trophoblast invasion, while migration showed no significant change. These findings suggest that HOOK2 may serve as a promising early biomarker for PE by modulating trophoblast invasiveness under altered hemodynamic conditions, with potential to improve risk stratification and personalized monitoring in pregnancy.

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive form of epithelial ovarian cancer, characterized by high recurrence rates and poor clinical outcomes. In this study, we identify molecular signatures associated with recurrence by conducting integrative transcriptomic and proteomic analyses on paired primary and recurrent HGSOC tissues from 34 patients. RNA sequencing and proteomic profiling revealed 185 differentially expressed genes (DEGs) and 36 differentially expressed proteins (DEPs) linked to recurrence. Pathway Enrichment and Ingenuity Pathway Analysis highlighted the involvement of immune cell trafficking, cell signaling, and MAPK pathway activation in recurrent tumors. Survival analysis identified seven DEGs significantly correlated with recurrence-free survival; among these, IL7R, IRF8, and PTPRC were upregulated in recurrent tumors and associated with poor prognosis, while NSG1 was downregulated and linked to favorable outcomes. Immunohistochemistry validated the differential expression of these markers at the protein level. Proteomic analysis demonstrated that recurrent tumor-specific DEGs are functionally linked to MAPK signaling. Co-expression analyses revealed dynamic regulatory interactions between DEGs and DEPs, suggesting context-dependent molecular shifts during recurrence. This integrative multi-omics approach reveals key molecular alterations underlying HGSOC recurrence and identifies IL7R, IRF8, PTPRC, and NSG1 as potential prognostic biomarkers and therapeutic targets. Our findings provide a foundation for targeted strategies to improve outcomes for patients with recurrent HGSOC.

Background/Objectives: S100A14 has been implicated in cellular signaling and tissue remodeling, but its relationship with histologic chorioamnionitis (HCA) remains unknown. We evaluated its placental expression and discriminatory performance for HCA in preterm birth. Methods: This retrospective cohort included 233 women with singleton spontaneous preterm births. Placental tissues were evaluated by immunohistochemistry for S100A14, MMP-2, ERK, and p38. Expression was compared by HCA status, and correlations were evaluated using Spearman coefficients. Multivariable logistic regression was adjusted for gestational age at delivery and preterm prelabor rupture of membranes (PPROM) status. Discriminatory performance was assessed using receiver operating characteristic analysis. Results: S100A14 scores were higher in placentas with HCA than without HCA (5.61 vs. 2.97, p < 0.001) and remained independently associated with HCA after adjustment (adjusted odds ratio per 1-point increase, 1.50; 95% confidence interval, 1.31–1.71; p < 0.001). MMP-2 expression was also elevated in HCA, whereas ERK and p38 expression did not differ by HCA status. S100A14 correlated most strongly with MMP-2 (ρ = 0.531, p < 0.001). Among 173 participants with complete data, the areas under the curve were 0.780 for placental S100A14, 0.717 for placental MMP-2, and 0.660 for maternal serum CRP at admission; the difference between S100A14 and CRP was statistically significant (p = 0.023), whereas the difference between S100A14 and MMP-2 was not (p = 0.126). At an optimal cutoff of 5.0, sensitivity was 55.2% and specificity was 80.2%. Conclusions: Placental S100A14 expression was independently associated with HCA and showed moderate tissue-level discriminatory ability for HCA. Its modest sensitivity limits its utility as a stand-alone diagnostic marker. Further studies are required to determine whether S100A14 or related molecular signals can be detected and validated in specimens obtainable before delivery.