Coexpression of lncRNAs MALAT1, HOTAIR and PVT1 with pro-infammatory cytokines in the formation of a platinum-resistant phenotype of ovarian cancer

Background. Expression of the main mediators of infammatory signaling – cytokines and long non-coding RNAs (lncRNAs) – determines the course of the tumor process and the formation of a platinum-insensitive phenotype in ovarian cancer.
The aim of the study was to evaluate the co-expression of long non-coding RNAs HOTAIR, MALAT1, PVT1 with proinfammatory cytokines in blood plasma during the formation of a platinum-insensitive phenotype in ovarian cancer.
Material and Methods. The study included 46 patients with primary ovarian cancer treated at the Ulyanovsk Oncology Center in 2018–2020. RNA was isolated from 2 ml of patients’ blood plasma before treatment, followed by reverse transcription and polymerase chain reaction to analyze the expression of HOTAIR, MALAT1, and PVT1. Plasma levels of the cytokines IL-1β, -10, -17A, and -18 were also determined. Ovarian cancer patients were divided into 2 groups based on the duration of the platinum-free interval.
Results. Plasma expression of long non-coding RNAs (lncRNAs) HOTAIR, MALAT1, and PVT1 was found to be signifcantly higher in patients with ovarian cancer than in patients with benign ovarian tumors. Plasma HOTAIR expression was also higher in stages III–IV ovarian cancer compared to stages I–II. Patients with platinum-insensitive ovarian cancer had signifcantly lower levels of IL-17A and IL-10 compared to patients in the comparison group, but higher levels of IL-1β and IL-10 compared to patients in the platinum-sensitive group. A correlation was found between the levels of lncRNA MALAT1 and IL-18.
Conclusion. The serum expression level of PVT1 lncRNA in ovarian cancer patients correlates with progression-free survival and allows for assessing the likelihood of disease recurrence. Serum coexpression of MALAT1 and IL-18 lncRNAs can be used as a predictive marker for identifying platinuminsensitive ovarian cancer. Their combined overexpression with proinfammatory cytokines and IL-1β before chemotherapy has prognostic potential as a marker of platinum resistance in ovarian cancer. A prognostic model for assessing the risk of cancer progression in the frst 6 months after diagnosis includes MALAT1 and HOTAIR expression data at the start of therapy and serum IL-1β and -18 levels. A K-value above 1.65 indicates a high risk of disease progression.

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