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Objective: To investigate the dynamic changes of serum carbohydrate antigen 125 (CA125) and human epididymal protein 4 (HE4) levels before and after surgery and during chemotherapy, and their relationship with progression-free survival (PFS) and platinum sensitivity in patients with ovarian cancer. Methods: A retrospective analysis was conducted on serum CA125 and HE4 levels before surgery, before chemotherapy, and at least twice during chemotherapy in standardized treated patients with ovarian cancer in the gynecologic oncology department of the First People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine. Data on platinum drug sensitivity and PFS were collected. The main statistical methods included chi-square test, t-test, logistic regression analysis, and Cox proportional hazards regression analysis. Results: The analysis of 117 patients with high-grade serous ovarian cancer suggested that CA125 and HE4 positivity were associated with higher stage, greater ascites volume, unsatisfactory surgical debulking, and positive ascites cytology. Cox regression analysis verified that both CA125 and HE4 are prognostic risk factors (OR=4.29, P=0.010; OR=1.77, P=0.049). Patients with both CA125 and HE4 positive and those with only CA125 positive showed no significant difference in prognosis (P > 0.05). The half-life of CA125 and HE4 were calculated using the formula t1/2=t1 [/2×lg (c1/c2)]. The optimal cut-offs for preoperative and postoperative CA125 and HE4, and the half-life of CA125 and HE4 were determined by X-tile and were 436 U/L, 400 pmol/L, 12 U/L, 35 pmol/L, 21 days, and 25 days, respectively. The prognostic analysis showed that except for the lowest value of HE4, all other factors were related to prognosis. The highest HR value was 3.28 for CA125 half-life >21 days, with a decrease of 57.5% in median PFS (P < 0.001). The area under the curve (AUC) was calculated by plotting the receiver operating characteristic (ROC) curve. ROC curve analysis showed that CA125 half-life >21 days (AUC=0.76), CA125 lowest value >12 U/L (AUC=0.70), and failure of CA125 to return to normal after the third cycle of chemotherapy (AUC=0.71) have certain clinical value for predicting recurrence within three years, with sensitivities of 71.8%, 68.3%, and 68.2%, and specificities of 79.6%, 71.7%, and 72.6%, respectively. Conclusion: CA125 half-life, the lowest value of CA125 during chemotherapy, CA125 not returning to normal after the third cycle of chemotherapy, and having ≥ 2 positive indicators among the 6 indicators have certain clinical value in predicting recurrence within 3 years. Further exploration is needed to assess their value in predicting platinum sensitivity. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of miR-155-5p on the sensitivity of ovarian cancer cell UWB1.289 to PARP inhibitors, and to explore the possible molecular mechanism. Methods: qRT-PCR was used to detect the expression of miR-155-5p in BRCA1/2-mutated and non-BRCA1/2-mutated ovarian cancer tissues and ovarian cancer cells. Cell transfection, qRT-PCR and Western Blot techniques were used to detect the expression levels of miR-155-5p, as well as homologous recombination repair-related genes SIRT1 and BRG1 in ovarian cancer cell UWB1.289,which were transfected with miR-155-5p mimics or miR-155-5p inhibitor. The targeting of miR-155-5p to SIRT1 and BRG1 were verified by dual-luciferase reporter gene assay. The effect of miR-155-5p on the sensitivity of PARP inhibitors in ovarian cancer cell UWB1.289 was detected by CCK-8. Results: Compared with ovarian cancer tissues and ovarian cancer cells without BRCA1/2 mutation, miR-155-5p was lowly expressed in ovarian cancer tissues and cells with BRCA1/2 mutation. Transfection of miR-155-5p mimics could increase the expression of miR-155-5p in ovarian cancer cell UWB1.289, while reducing the expression of homologous recombination repair-related genes SIRT1 and BRG1; transfection of miR-155-5p inhibitor could down-regulate the expression of miR-155-5p in ovarian cancer cell UWB1.289, while increasing the expression of SIRT1 and BRG1. Further, the dual-luciferase reporter gene assay confirmed that miR-155-5p had specific targeted binding sequences to SIRT1 and BRG1. Compared with the control group, interfering with genes related to homologous recombination repair could enhance the sensitivity of ovarian cancer cell UWB1.289 to PARP inhibitors, and overexpression of miR-155-5p could also enhance the sensitivity of ovarian cancer cell UWB1. 289 to PARP inhibitors. Conclusion: miR-155-5p could enhance the sensitivity of ovarian cancer cell UWB1.289 to PARP inhibitors by affecting homologous recombination repair genes. [ABSTRACT FROM AUTHOR]

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Copyright of Shandong Medical Journal is the property of Shandong Medical Health Newspapers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)