Abstract 25P
Background
Epithelial ovarian cancer (EOC) is a disease found mainly in advanced stages and difficult to treat. The study of the expression and methylation of miRNA genes can become the basis for the development of potential new diagnostic and prognostic markers of EOC, as well as the basis for the development of targeted anticancer therapy.
Methods
80 paired samples of EOC (ovarian serous adenocracinoma) were obtained from the National Medical Research Center of Oncology named after N.N. Blokhin. MicroRNA expression was assessed by TaqMan-qPCR with kits from Applied Biosystems, USA. Analysis of methylation of promoter CpG islands of microRNA genes was carried out using bisulfite conversion followed by methyl-specific PCR.
Results
The methylation frequency in the tumor was higher than in paired norm for 10 microRNA genes (MIR-124-1, -124-2, -124-3, -125B-1, -127, -129-2, -132, -137, -193A and -339; p ≤ 5×10-4). ROC analysis showed that a combination of 4 microRNA genes (MIR-124-2, -127, -129-2, -137) can be proposed as a panel of EOC detection markers with sensitivity (Sn) 80%, specificity (Sp) 82 %, AUC=0.86. The combination of miRNA genes (MIR-193A, -129-2, -137) was characterized by Sn=90%, Sp=75% and AUC=0.90. For 5 out of 12 microRNAs studied, a high frequency of reduced expression was observed: miR-125b-5p - in 59% of tumor samples compairing to paired norms, miR-129-5p - in 55%, miR-132-3p - in 55%, miR-137 - in 52% , and miR-193a-5p in 66% (p ≤ 0.05). The correlation of changes in the expression of 12 microRNAs (miR-124-3p, -125b-5p, -127-5p, 129-5p, -132-3p, -137, -148a-3p, -191-5p, -193a-5p, -203a, -339-3p and -375) and changes in methylation of the genes encoding them rs=0.67-0.97 (according to Spearman), p ≤ 10-4.
Conclusions
The role of methylation in the regulation of the expression of 12 microRNAs and the association of the methylation status of 10 microRNA genes with EOC metastasis were revealed. 5 microRNAs downregulated by hypermethylation may find use as potential targets for EOC therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The state task FGFU-2022-0007 of the Ministry of Science and Higher Education of the Russian Federation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
24P - Fibroblast growth factor receptor (FGFR) as a target for epigenetic therapies: A case review for a new approach to target tumors with somatic mutations/amplifications of FGFR
Presenter: M. Nezami
Session: Cocktail & Poster Display session
Resources:
Abstract
26P - 3MST: A potential workhorse in H2S signaling trimmed by microRNA-548 in breast cancer
Presenter: Alyaa Dawoud
Session: Cocktail & Poster Display session
Resources:
Abstract
29P - A phase I, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, antitumor activity of QL1604, a humanized anti-PD-1 mAb, in patients with advanced solid tumors
Presenter: Yun Fan
Session: Cocktail & Poster Display session
Resources:
Abstract
30P - Deep learning approach for discovering new predictive histological features of immunotherapy response
Presenter: Saima Ben Hadj
Session: Cocktail & Poster Display session
Resources:
Abstract
32P - Clinical efficacy and safety of an immune checkpoint inhibitor in combination with regorafenib therapy as second-line regimen for patients with unresectable hepatocellular carcinoma
Presenter: Jinpeng Li
Session: Cocktail & Poster Display session
Resources:
Abstract
33P - Nomogram to predict survival of patients with unresectable melanoma receiving immune checkpoint inhibitors
Presenter: Eftychia Chatziioannou
Session: Cocktail & Poster Display session
Resources:
Abstract
34P - Targeting LSD1 rescues MHC-I antigen presentation and overcomes resistance to PD-L1 checkpoint blockade in small cell lung cancer
Presenter: Evelyn Nguyen
Session: Cocktail & Poster Display session
Resources:
Abstract
36P - Therapeutic vaccination with HPV-16 oncoproteins fused into a checkpoint modifier of early T cell activation protects against HPV-associated tumors in a preclinical model
Presenter: Susan Currie
Session: Cocktail & Poster Display session
Resources:
Abstract
37P - Dose transition pathways for time-to-event continual reassessment method (TITE-CRM): Will imposing a waiting time result in better performance?
Presenter: Zhulin Yin
Session: Cocktail & Poster Display session
Resources:
Abstract
38P - Locoregional radiotherapy improves survival outcomes in de novo metastatic nasopharyngeal carcinoma treated with chemoimmunotherapy
Presenter: Yujun Hu
Session: Cocktail & Poster Display session
Resources:
Abstract