Development and validation of MRI-based scoring models for predicting placental invasiveness in high-risk women for placenta accreta spectrum.

OBJECTIVES: To develop and validate MRI-based scoring models for predicting placenta accreta spectrum (PAS) invasiveness. MATERIALS AND METHODS: This retrospective study comprised a derivation cohort and a validation cohort. The derivation cohort came from a systematic review of published studies evaluating the diagnostic performance of MRI signs for PAS and/or placenta percreta in high-risk women. The significant signs were identified and used to develop prediction models for PAS and placenta percreta. Between 2016 and 2021, consecutive high-risk pregnant women for PAS who underwent placental MRI constituted the validation cohort. Two radiologists independently evaluated the MRI signs. The reference standard was intraoperative and pathologic findings. The predictive ability of MRI-based models was evaluated using the area under the curve (AUC). RESULTS: The derivation cohort included 26 studies involving 2568 women and the validation cohort consisted of 294 women with PAS diagnosed in 258 women (88%). Quantitative meta-analysis revealed that T2-dark bands, placental/uterine bulge, loss of T2 hypointense interface, bladder wall interruption, placental heterogeneity, and abnormal intraplacental vascularity were associated with both PAS and placenta percreta, and myometrial thinning and focal exophytic mass were exclusively associated with PAS. The PAS model was validated with an AUC of 0.90 (95% CI: 0.86, 0.93) for predicting PAS and 0.85 (95% CI: 0.79, 0.90) for adverse peripartum outcome; the placenta percreta model showed an AUC of 0.92 (95% CI: 0.86, 0.98) for predicting placenta percreta. CONCLUSION: MRI-based scoring models established based on quantitative meta-analysis can accurately predict PAS, placenta percreta, and adverse peripartum outcome. CLINICAL RELEVANCE STATEMENT: These proposed MRI-based scoring models could help accurately predict PAS invasiveness and provide evidence-based risk stratification in the management of high-risk pregnant women for PAS. KEY POINTS: • Accurately identifying placenta accreta spectrum (PAS) and assessing its invasiveness depending solely on individual MRI signs remained challenging. • MRI-based scoring models, established through quantitative meta-analysis of multiple MRI signs, offered the potential to predict PAS invasiveness in high-risk pregnant women. • These MRI-based models allowed for evidence-based risk stratification in the management of pregnancies suspected of having PAS.

Circular RNA ACTR2 activates M2 polarization of macrophages through activating Yes-associated protein signalling and contributes to renal fibrosis.

Macrophages, associated with their heterogenous and dynamic polarization status, actively shape the development of renal fibrosis (RF). In this study, we revealed the significance of a signalling axis, circular RNA ACTR2 (circACTR2)/miR-200c/Yes-associated protein (YAP), in regulating macrophage polarization and the development of RF. A unilateral urethral obstruction (UUO)-induced RF model was established in vivo. In vitro, interferon-γ (IFNγ) and interleukin (IL)-4 were applied to induce M1 and M2 polarization, respectively. The abundance of M1 and M2 macrophages were examined by immunofluorescence (IF) or flow cytrometry on markers specific for each subtype. Expressions of circACTR2, miR-200c and YAP were measured by quantitative real-time-polymerase chain reaction and/or Western blotting. Interactions between circACTR2, miR-200c and YAP were examined by combining luciferase assay, RNA immunoprecipitation and IF. Impact of targeting circACTR2 on RF and macrophage polarization was also examined in vivo. UUO-induced RF was associated with increased M1 and M2 macrophages, up-regulations of circACTR2 and YAP and the down-regulation of miR-200c in the obstructed kidney. circACTR2 was essential for IL-4-induced M2 polarization, but not IFNγ-induced M1 polarization. This activity of circACTR2 was mediated by sponging miR-200c and activating the downstream YAP signalling. In vivo, knocking down circACTR2 boosted miR-200c expression, reduced YAP level, lowered M2 macrophages in obstructed kidney and ameliorated UUO-induced RF. circACTR2, by targeting and sponging miR-200c, activates YAP signalling, stimulates M2 macrophage polarization and promotes the development of RF. Therefore, targeting circACTR2 may benefit the treatment of RF.

[Molecular markers derived from ovarian cancer and its correlation with the types of oviductal epithelial lesions].

OBJECTIVE: To explore the role of P53, pairing box gene 8 antibody (PAX8), and calcium omentum protein (Calretinin) in the origin of epithelial ovarian cancer.
 Methods: A total of 63 tissue samples of ovarian tumor and fallopian tubes were collected. Immunohistochemistry methods were used to analyze the expression of P53, PAX8, and Calretinin. The relationship between these protein levels and the classification of ovarian tumors was evaluated.
 Results: In epithelial ovarian cancer, the P53 or PAX8 was correlated with the occurrence of high-grade carcinoma, while the calretinin was correlated with the occurrence of low-grade carcinoma (P<0.05). The combination of PAX8 with Calretinin was correlated with the grade of ovarian tumor (P<0.05). The combination of P53 with Calretinin was correlated with the grade of tumor (P<0.05). The combination of P53 with PAX8 was correlated with the grade of tumor (P<0.05). The expression of P53 in fallopian tubes was correlated with the malignant degree of epithelial ovarian cancer (P<0.05). The degree of fallopian tube lesions in patients with ovarian cancer was correlated with epithelial ovarian cancer. The malignant lesions of tubal epithelium was correlated with high-grade carcinoma, while the normal or atypical hyperplasia of tubal epithelium was correlated with low-grade carcinoma (P<0.05).
 Conclusion: P53 and Calretinin combined with PAX8 show a synergistic effect on the differentiation of epithelial ovarian cancer grade. The morphology of HE and the expression of TP53 in the fallopian tube epithelium play an auxiliary role in the diagnosis of epithelial ovarian cancer.

Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer.

BACKGROUND: Ovarian cancer is an epithelial malignancy that intrigues people for its poor outcome and lack of efficient treatment, while methylation is an important mechanism that have been recognized in many malignancies. In this study, we attempt to assess abnormally methylated gene markers and pathways in ovarian cancer by integrating three microarray datasets. METHODS: Three datasets including expression (GSE26712 and GSE66957) and methylation (GSE81224) datasets were accessed. GEO2R platform was used to detect abnormally methylated-differentially expressed genes. Protein-protein interaction (PPI) networks were built and analysed for hypermethylated and hypermethylated differentially expressed genes using Cytoscape software and Mcode app. GEPIA and cBioPortal platforms were used to validate the expression of the hub genes and the correlation between their mRNA expressions and methylation levels. Kaplan Meier-plotter platform were used to assess the prognostic significance of the hub genes. RESULTS: Six hundred eighty-one hypomethylated-upregulated genes were detected and involved in Rap1 signaling pathway, biosynthesis of amino acids, endocrine resistance, apoptosis, pathways in cancer. The hub genes were TNF, UBC, SRC, ESR1, CDK1, PECAM1, CXCR4, MUC1, IKBKG. Additionally, 337 hypermethylated-downregulated genes were detected and involved in pathways in cancer, focal adhesion, sphingolipid signaling pathway, EGFR tyrosine kinase inhibitor resistance, cellular senescence. The hub genes were BDNF, CDC42, CD44, PPP2R5C, PTEN, UBB, BMP2, FOXO1, KLHL2. TNF, ESR1, MUC1, CD44, PPP2R5C, PTEN, UBB and FOXO1 showed significant negative correlation between their mRNA expressions and methylation levels. TNF, ESR1 and FOXO1 showed prognostic significance. CONCLUSIONS: Two novel gene networks were found for ovarian cancer. TNF, ESR1, MUC1 and FOXO1 are our candidate genes that might take part in ovarian cancer progression in an epigenetic approach, TNF, ESR1 and FOXO1 may serve as potential markers for ovarian cancer prognosis evaluation.

Bilateral kidneys involvement of collecting duct carcinoma with cystic change: A case report.

RATIONALE: Collecting duct carcinoma (CDC) is a rare neoplasm arising from the collecting duct and should be distinguished from other renal cell carcinomas that mostly originated from the proximal tubular epithelium and tumors originated from the urothelium. It usually occurs in unilateral kidney, sometimes found with cystic change. PATIENT CONCERNS: We present the case of a 53-year-old male suffering from repeated bilateral flank pain for 6 months, increased pain with dysuria for 5 days. DIAGNOSIS: Ultrasound showed 2 similar hybrid echo masses in bilateral kidneys with enlarged lymph nodes surrounded, which accords with magnetic resonance imaging (MRI), and intraoperative biopsy reported malignancy. INTERVENTIONS: An exploratory operation was performed and the mass on the left kidney was removed, but pathological result reported collecting duct carcinoma according to the morphological features and immunohistochemical tests. Also postsurgery positron emission tomography-computed tomography (PET-CT) confirmed the mass on the left kidney is also a lesion of CDC. OUTCOMES: The patient refused chemotherapy and had an overall survival of 7 months. LESSONS: We presented a case of CDC involving bilateral kidneys with cystic change; this is the first case of bilateral renal occurrence with cystic change to our knowledge. Because of CDC's rapid growth and the lack of effective adjuvant treatment after surgery, the prognosis is poor and the diagnosis should be made carefully.

Ovarian cancer cell-secreted exosomal miR-205 promotes metastasis by inducing angiogenesis.

Background: By providing oxygen, nutrients and metastatic conduits, tumour angiogenesis is essential for cancer metastasis. Cancer cell-secreted microRNAs can be packaged into exosomes and are implicated in different aspects of tumour angiogenesis. However, the underlying mechanisms are incompletely understood. Methods: The GEPIA database and in situ hybridization assay were used to analyse expression of miR-205 in ovarian tissues. Immunohistochemistry was performed to examine the relationship between miR-205 and microvessel density. Expression of circulating miR-205 was evaluated by RT-PCR and GEO database analysis. Co-culture and exosome labelling experiments were performed to assess exosomal miR-205 transfer from ovarian cancer (OC) cells to endothelial cells ECs. Exosome uptake assays were employed to define the cellular pathways associated with the endocytic uptake of exosomal miR-205. The role of exosomal miR-205 in angiogenesis was further investigated in vivo and in vitro. Western blotting and rescue experiments were applied to detect regulation of the PTEN-AKT pathway by exosomal miR-205 in ECs. Results: miR-205 was up-regulated in OC tissues, and high expression of miR-205 was associated with metastatic progression in OC patients. Moreover, miR-205 was highly enriched in cancer-adjacent ECs, and up-regulation of miR-205 correlated positively with high microvessel density in OC patients. Importantly, miR-205 was markedly enriched in the serum of OC patients, and a high level of miR-205 in circulating exosomes was associated with OC metastasis. In addition, OC-derived miR-205 was secreted into the extracellular space and efficiently transferred to adjacent ECs in an exosome-dependent manner, and the lipid raft-associated pathway plays an important role in regulating uptake of exosomal miR-205. Exosomal miR-205 from OC cells significantly promoted in vitro angiogenesis and accelerated angiogenesis and tumour growth in a mouse model. Furthermore, we found that exosomal miR-205 induces angiogenesis via the PTEN-AKT pathway. Conclusion: These findings demonstrate an exosome-dependent mechanism by which miR-205 derived from cancer cells regulates tumour angiogenesis and implicate exosomal miR-205 as a potential therapeutic target for OC.