Atike Gökçen Demiray

Characterization of lncRNAs contributing to drug resistance in epithelial ovarian cancer

Abstract Epithelial ovarian cancer (EOC) is the second leading cause of death among women with gynecological cancers, particularly in high-income countries. Despite significant advancements in molecular oncology and an initially positive response to primary chemotherapy, the development of drug resistance remains a major challenge in the effective management of EOC. Consequently, there is an urgent need for innovative biological markers that can enable early diagnosis and provide more accurate predictions of recurrence risk in ovarian cancer patients. This study investigated the expression profiles of seven specific long noncoding RNAs (lncRNAs)—SNHG7, TUG1, XIST1, PRLB, TLR8-AS1, ZFAS1, and PVT1—associated with epithelial ovarian cancer and their relationship with drug resistance. To achieve this, drug-resistant subtypes of aggressive EOC cell lines, including carboplatin/paclitaxel-resistant OVCAR3 and SKOV3 lines, were developed. The expression profiles of the selected lncRNAs were quantitatively analyzed using RT-qPCR across various ovarian cancer cell lines and in serum samples from 25 patients before chemotherapy, six months after treatment, and 23 healthy controls. The findings revealed that the target lncRNAs were significantly upregulated under drug-resistant conditions and in post-chemotherapy serum samples, suggesting their involvement in a complex regulatory network. These results highlight the critical roles of lncRNAs in the progression and treatment response of EOC, positioning them as potential therapeutic targets and biomarkers for early diagnosis and treatment stratification. Identifying reliable lncRNA biomarkers could enable the early detection of patients at risk for developing drug resistance, thereby facilitating personalized treatment strategies to improve patient outcomes and survival rates.

The relation of CD3, CD4, CD8 and PD-1 expression with tumor type and prognosis in epithelial ovarian cancers

Ovarian cancer is a heterogeneous disease, where chronic inflammation plays a key role in carcinogenesis. In this study, it is aimed to analyze the relationship with prognosis and chemotherapy response to clinicopathologicalnvariables in epithelial ovarian cancers such as proliferation of PD-1 +, CD8 +, CD4 +, CD3 + T-lymphocytes infiltrating the tumor and tumor stroma. Seventy-six cases diagnosed with primary epithelial ovarian tumor from biopsy or surgical resection materials were included in the study. Immunreactivity of CD3, CD4, CD8, PD1 was evaluated immunohistochemically in lymphocytes in tumor infiltrating lymphocytes and stromal lymphocytes. Seventeen (22.4%) of the cases were Type I, 59 (77.6%) of them were Type II ovarian carcinoma. PD-1 positivity was observed in stromal and intraepithelial lymphocytes in 22 (28.9%) of 76 cases. In the presence of PD-1 + T-lymphocytes that infiltrate tumor and stroma, disease-free survival are shorter (p = 0.037). The presence of stromal CD4 + and CD8 + T-lymphocytes was more common in late stage patients (p = 0.012, p = 0.036; respectively). The disease-free and overall survival rate was statistically significantly shorter in the presence of CD8 + T lymphocytes (p = 0.009, p = 0.003; respectively). CD3, CD4 and CD8 may contribute to PD-1 mediated tumor control. Anti PD-1 therapy may be an alternative to chemotherapy in PD-1 positive patients. Identifying patients who do not respond to chemotherapy through PD-1 expression prior to immunotherapy will help develop potential personalized immunotherapy.