[The expression of MFAP5 in ovarian cancer and its effect on cancer cell proliferation, metastasis and drug resistance].

Objective: To investigate the expression of microfibril-associated protein 5 (MFAP5) in ovarian cancer and its influence on malignant behavior of ovarian cancer cells. Methods: GEPIA, CSIOVDB and Kaplan-Meier Plotter online databases were used to analyze the expression of MFAP5 in various tumor tissues, especially in ovarian cancer. Immunohistochemistry was used to detect the expression level of MFAP5 in ovarian cancer tissue chip (The tissue microarray was commissioned to Zhongke Guanghua [Xi'an] Intelligent Biotechnology Co., Ltd. for processing. The specimens were sourced from Henan Provincial People's Hospital from January 2018 to March 2023), and the relationship between MFAP5 expression and the clinical characteristics of patients with ovarian cancer was analyzed using SPSS software. Kaplan-Meier Plotter online database was used to analyze the relationship between MFAP5 expression and survival prognosis of ovarian cancer patients. The ovarian cancer data sets GSE9891 and TCGA594 were downloaded from GEO and TCGA respectively, and ssGSEA was used to analyze the scores of gene sets related to epithelial mesenchymal transition, migration and invasion in ovarian cancer data sets. Next, the relationship between MFAP5 expression and the above scores was analyzed using GraphPad Prism. The expression of MFAP5 in normal fibroblasts (NFs) and cancer associated fibroblasts (CAFs) was verified by western blot. MFAP5 expression in CAFs was reduced by MFAP5-si RNA, and influence of CAFs with high or low expression of MFAP5 on malignant behavior of ovarian cancer cell SKOV3 was verified by transwell test. The influence of CAFs with high or low expression of MFAP5 on epithelial mesenchymal transition markers of ovarian cancer cell SKOV3 was verified by western blot. The CCK8 assay and 3D co-culture model were used to verify the effects of CAFs with high and low MFAP5 expression on the chemoresistance of ovarian cancer cells SKOV3. Transwell assay, western blot, and 3D co-culture model were used to explore and verify the related pathways through which MFAP5 affects the malignant behavior and drug resistance of ovarian cancer cells SKOV3. Results: Online data analysis showed that the expression of MFAP5 in ovarian cancer tissue was significantly higher than that in normal ovarian tissue (P＜0.001). Immunohistochemistry showed that the expression of MFAP5 was mainly concentrated in ovarian cancer stroma, and the later stage and the higher grade ovarian cancer tissues showed higher MFAP5 expression. Survival analysis showed that the high expression of MFAP5 was related to the poor prognosis of patients, and it was only significant in later stages and higher grades. ssGSEA analysis showed that the expression of MFAP5 was positively correlated with the scores of gene sets related to epithelial-mesenchymal transition, migration and invasion of ovarian cancer. In vitro experiments showed that reducing the expression of MFAP5 in CAFs could not only partially reduce its supportive effect on the malignant behaviors such as migration and invasion of ovarian cancer epithelial cells SKOV3 (The number of migrating cells in the control group, si-NC group, and si-MFAP5-group was 73.44±7.80, 199.74±18.26, and 91.21±6.70, respectively. The number of invading cells in the control group, si-NC group, and si-MFAP5-group was 61.62±8.76, 174.81±15.23, and 67.17±9.83, respectively), but also increase the sensitivity of ovarian cancer epithelial cells SKOV3 to chemotherapy and maintenance therapy. Further research showed that MFAP5 could activate the AKT signaling pathway in ovarian cancer cells SKOV3, and inhibiting the AKT pathway could block the supportive effect of MFAP5 on the malignant behavior and drug resistance of ovarian cancer cells. Conclusions: MFAP5 is highly expressed in ovarian cancer, especially in the stromal tissue of ovarian cancer, where the expression level is the highest. High expression of MFAP5 often indicates a poor prognosis for ovarian cancer patients. By reducing the expression of MFAP5 in CAFs, the supportive effect on the malignant biological behavior and drug resistance of ovarian cancer epithelial cells can be weakened. The underlying mechanism of this phenomenon may be related to the blockade of the AKT signaling pathway in ovarian cancer cells.