Sufen Zhao

Radiomics Signatures Based on Computed Tomography for Noninvasive Prediction of CXCL10 Expression and Prognosis in Ovarian Cancer

ABSTRACTBackgroundOvarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with malignant ascites and even observed widespread metastasis or distant spread.AimsWe aimed to develop and identify radiomics models according to computed tomography (CT) for preoperative prediction of CXCL10 expression and prognosis in patients with OC.MethodsGenomic data with CT images and corresponding clinicopathological parameters were extracted from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). To analyze the prognosis, we carried out the univariate Cox regression analysis (UCRA), multivariate Cox regression analysis (MCRA), and Kaplan–Meier (KM) analysis. For the data reduction, logistic regression, operator regression, least absolute shrinkage selection, radiomic feature construction, and feature selection were utilized. The predictive performance of the radiomic signatures was assessed using the analyses of the receiver operating characteristic (ROC) curve, decision curve (DCA), and precision‐recall (PR) curve. To evaluate the correlation between the radiomic score (Rad‐score) and CXCL10 expression, the Wilcoxon rank‐sum test was applied.ResultsThree radiomics models effectively predicted CXCL10 expression levels (AUC = 0.791, 0.748, and 0.718 for the set of training; AUC = 0.761, 0.746, and 0.701 for the set of validation). A higher Rad‐score significantly correlated with upregulated CXCL10 expression.ConclusionCXCL10 expression can be predicted noninvasively and preoperatively via radiomic signatures based on contrast‐enhanced CT images.

CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer

Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-β-catenin signalling pathway. Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-β-catenin signalling pathway. The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-β-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Endothelial cell specific molecule 1 promotes epithelial-mesenchymal transition of cervical cancer via the E-box binding homeobox 1

Objective To investigate the mechanism of endothelial cell specific molecule 1 (ESM1) promoting cervical cancer cell proliferation and EMT characteristics through zinc finger E-box binding homeobox 1 (ZEB1)/EMT pathway. Methods The correlation between ESM1 expression and prognosis of cervical cancer patients was analyzed by bioinformatics. SiHa, HeLa cell lines and corresponding control cell lines with stable ESM1 expression were obtained. Cell proliferation ability was detected by CCK-8 assay. The invasion and migration ability of Hela and SiHa cells were detected by Transwell assay and scratch closure assay. Expressions of EMT-related markers E-cadherin and Vimentin were detected by real-time PCR. The ability of silenced ESM1 to tumor formation in vivo was detected by tumor formation in nude mice. The effects of aloe-emodin on inhibit ESM1 expression and its inhibitory effect on cervical cancer cells in vitro and in vivo were analyzed by the same method. Results ESM1 was highly expressed in cervical cancer, and the high expression of ESM1 was associated with poor prognosis of cervical cancer patients. CCK-8 results showed that the proliferation, invasion and migration of Hela and SiHa cells were significantly reduced after siRNA interfered with ESM1 expression. Overexpression of ESM1 promoted the proliferation and migration of cervical cancer cells. Mechanism studies have shown that the oncogenic effect of ESM1 is realized through the ZEB1/PI3K/AKT pathway. High throughput drug screening found that aloe-emodin can target ESM1. Inhibitory effect of aloe emodin on ESM1/ZEB1/EMT signaling pathway and cervical cancer cells. Conclusion The silencing of ESM1 expression may inhibit the proliferation, invasion, metastasis and epithelial-mesenchymal transformation of cervical cancer cells by inhibiting ZEB1/PI3K/AKT. Aloe-emodin is a potential treatment for cervical cancer, which can play an anti-tumor role by inhibiting ESM1/ZEB1.