Serum expression levels of HOTAIR and miR-646 in endometrial cancer

Rizki Harismunandar; Hande Karpuzoğlu; Yağmur Minareci; Hamdullah Sözen; Samet Topuz; Canan Küçükgergin; A Fatih Aydin

doi:10.3892/ol.2025.15443

Serum expression levels of HOTAIR and miR-646 in endometrial cancer

Oncol Lett. 2025 Dec 30;31(2):90. doi: 10.3892/ol.2025.15443. eCollection 2026 Feb.

Authors

Rizki Harismunandar¹, Hande Karpuzoğlu¹, Yağmur Minareci², Hamdullah Sözen², Samet Topuz², Canan Küçükgergin¹, A Fatih Aydin¹

Affiliations

¹ Department of Medical Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey.
² Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey.

Abstract

Endometrial cancer (EC) is the fourth most common malignancy in women in high-income countries and the sixth globally, with ~417,000 new cases and ~97,370 mortalities reported worldwide in 2020. Its incidence has increased by >130% over the past 30 years, due to advances in FIGO-based staging systems and earlier detection. However effective non-invasive biomarkers for early diagnosis and staging are limited. Non-coding RNAs (ncRNAs), particularly long ncRNAs (lncRNAs) and microRNAs (miRs), are critical regulators in the biology of cancer, and may potentially serve as novel diagnostic and prognostic biomarkers. In the present study, serum levels of the lncRNA Hox antisense intergenic RNA (HOTAIR) and the miR-646 were evaluated in 71 patients with EC and 62 matched healthy controls using reverse transcription-quantitative PCR. The results showed that the serum HOTAIR expression level was significantly increased in patients with EC compared with controls. This suggested that it may have potential as a diagnostic biomarker. Although overall miR-646 levels did not differ significantly between patients with EC and healthy controls, a notable reduction in miR-646 levels were observed in patients with advanced clinical T stages compared with those with early stages. This indicated an association with disease progression. Receiver operating characteristic curve analyses indicated that a serum HOTAIR level of 1.08 may distinguish patients with EC from healthy controls with 63.3% sensitivity and 61.2% specificity. Additionally, a miR-646 cut-off value of 0.655 differentiated patients with advanced-stage from early-stage EC with 72.7% sensitivity and 66.7% specificity. These findings suggested that serum HOTAIR may be a potential diagnostic biomarker and that miR-646 may be a potential indicator of disease progression in EC. However, further validation in larger patient cohorts and investigation of exosomal expression levels are necessary in order to assess the potential clinical relevance and therapeutic potential of HOTAIR and miR-646.

Keywords: Hox antisense intergenic RNA; endometrial cancer; long non-coding RNA; microRNA-646; non-coding RNAs; serum biomarkers.