Abstract LB315: Expression of <i>NOTCH3</i> and <i>DLK1</i> genes in tumor and exosome derived from patients with ovarian cancer and their epidemiological perspectives

Abstract Ovarian cancer is a complex and heterogenous disease with increasing incidence worldwide, and it is considered one of the most common gynecological malignancies due to its poorly known underlying molecular pathways. Currently, all subtypes presenting as adnexal masses are treated, diagnosed, and monitored according to the same principles. Therefore, differentiating between subtypes is important for effective management of this cancer. Among its subtypes, serous and mucinous ovarian cancers are particularly significant due to their distinct biological characteristics. Serous ovarian cancer, the most common and aggressive subtype, is associated with poor prognosis and high recurrence rates. Mucinous ovarian cancer, though less common, poses diagnostic and therapeutic difficulties due to its rarity and unique histological features. Notch signaling pathway is significantly altered in ovarian cancer where Notch3 is upregulated and associated with poor prognosis. It was reported overexpression of Delta-like 1 homolog (DLK1) was observed in serous subtype, and involved with ovarian carcinogenesis through activation of Notch signaling pathway and epithelial-mesenchymal transition. However, numerous studies have been conducted on the expression profile of Notch3 and DLK1, but no report was observed on the expression pattern of Notch3 and DLK1 in both serous and mucinous subtypes of ovarian cancer in Bangladesh. Therefore, we have investigated the expression of Notch3 and DLK1 in both serous and mucinous subtypes of ovarian tumor tissues derived from patients with ovarian cancer by real-time quantitative polymerase chain reaction (RT-qPCR). We also analyzed the expression of Notch3 and DLK1 in exosomes of sera from mucinous ovarian patients. Our study revealed that the expression of Notch3 was significantly higher in both serous and mucinous tumor tissues compared with their healthy ovarian tissues. Notch3 expression was also higher in exosomes of sera derived from the patients of mucinous tumor subtype. In contrast, DLK1 exhibits a higher level of expression in serous tumors subtype but a lower level in mucinous tumors subtype as well as in exosomes of sera from the patient with mucinous ovarian tumor. In addition, questionnaire analysis from the patients revealed high rates of early menstruation or late menopause, passive smoking, and consumption of betel leaf and dry fish consumers, providing insight into the risk factors. The findings suggest that DLK1 may be useful to distinguish serous and mucinous ovarian cancer subtypes. Analysis of the expression of these genes is progressing with the increasing number of serous and mucinous tumor tissues, and that would be helpful to conclude the results precisely. Citation Format: Tasnim Monoara Tanju, Mashrifa Khanam, Rupali Akter, Jubaida Haque Alam, Md. Omer Faruq, Farhana Yesmin, Kanchan Chakma, Robiul Hasan Bhuiyan. Expression of NOTCH3 and DLK1 genes in tumor and exosome derived from patients with ovarian cancer and their epidemiological perspectives [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB315.