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Article Open Access

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

  • Authors:
    • Rizki̇ Hari̇smunandar
    • Hande Karpuzoğlu
    • Yağmur Mi̇nareci̇
    • Hamdullah Sözen
    • Samet Topuz
    • Canan Küçükgergi̇n
    • A. Fati̇h Aydin
  • View Affiliations / Copyright

    Affiliations: Department of Medical Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey, Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey
    Copyright: © Hari̇smunandar et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 90
    |
    Published online on: December 30, 2025
       https://doi.org/10.3892/ol.2025.15443
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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.
View Figures

Figure 1

Differential expression levels of
HOTAIR and miR-646 according to tumour grade, stage, lymph node
involvement and recurrence status in patients with endometrial
cancer. (A) HOTAIR and (B) miR-646 expression levels in control vs.
patient groups. (C) HOTAIR and (D) miR-646 expression levels
according to tumour grade. Endometrial cancer was classified as low
grade (grades 1–2 endometrioid) and high grade (grade 3
endometrioid and non-endometrioid histology types). (E) HOTAIR and
(F) miR-646 expression levels according to tumour stage. Stages IA
and B were considered as early stages, while stages II–IV were
considered high stages. (G) HOTAIR and (H) miR-646 expression
levels according to lymph node involvement (negative vs. positive).
(I) HOTAIR and (J) miR-646 expression levels according to
recurrence status (recurrence-negative vs. recurrence-positive).
*P<0.05. HOTAIR, Hox antisense intergenic RNA; miR, microRNA;
ns, not significant.

Figure 2

Receiver operating characteristic
curve analyses for serum HOTAIR and miR-646. (A) To distinguish
patients with endometrial cancer from healthy controls, the cut-off
value for HOTAIR was 1.08. (B) To distinguish advanced from
early-stage endometrial cancer, the cut-off value for miR-646 was
0.655. HOTAIR, Hox antisense intergenic RNA; miR, microRNA; AUC,
area under the curve; SEN, sensitivity; SPE, specificity.

Figure 3

Overall survival analysis according
to serum HOTAIR and miR-646 expression levels. Patients with
endometrial cancer were divided into high- or low-expression groups
based on median relative expression levels. (A) Patients were
classed as ‘negative’ or ‘positive’ if the median relative HOTAIR
expression levels were <1.08 or ≥1.08, respectively. (B)
Patients were classed as ‘negative’ or ‘positive’ if the median
relative miR-646 expression levels were <0.655 or ≥0.655,
respectively. HOTAIR, Hox antisense intergenic RNA; miR,
microRNA.
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Copy and paste a formatted citation
Spandidos Publications style
Hari̇smunandar R, Karpuzoğlu H, Mi̇nareci̇ Y, Sözen H, Topuz S, Küçükgergi̇n C and Aydin AF: Serum expression levels of HOTAIR and miR‑646 in endometrial cancer. Oncol Lett 31: 90, 2026.
APA
Hari̇smunandar, R., Karpuzoğlu, H., Mi̇nareci̇, Y., Sözen, H., Topuz, S., Küçükgergi̇n, C., & Aydin, A.F. (2026). Serum expression levels of HOTAIR and miR‑646 in endometrial cancer. Oncology Letters, 31, 90. https://doi.org/10.3892/ol.2025.15443
MLA
Hari̇smunandar, R., Karpuzoğlu, H., Mi̇nareci̇, Y., Sözen, H., Topuz, S., Küçükgergi̇n, C., Aydin, A. F."Serum expression levels of HOTAIR and miR‑646 in endometrial cancer". Oncology Letters 31.2 (2026): 90.
Chicago
Hari̇smunandar, R., Karpuzoğlu, H., Mi̇nareci̇, Y., Sözen, H., Topuz, S., Küçükgergi̇n, C., Aydin, A. F."Serum expression levels of HOTAIR and miR‑646 in endometrial cancer". Oncology Letters 31, no. 2 (2026): 90. https://doi.org/10.3892/ol.2025.15443
Copy and paste a formatted citation
x
Spandidos Publications style
Hari̇smunandar R, Karpuzoğlu H, Mi̇nareci̇ Y, Sözen H, Topuz S, Küçükgergi̇n C and Aydin AF: Serum expression levels of HOTAIR and miR‑646 in endometrial cancer. Oncol Lett 31: 90, 2026.
APA
Hari̇smunandar, R., Karpuzoğlu, H., Mi̇nareci̇, Y., Sözen, H., Topuz, S., Küçükgergi̇n, C., & Aydin, A.F. (2026). Serum expression levels of HOTAIR and miR‑646 in endometrial cancer. Oncology Letters, 31, 90. https://doi.org/10.3892/ol.2025.15443
MLA
Hari̇smunandar, R., Karpuzoğlu, H., Mi̇nareci̇, Y., Sözen, H., Topuz, S., Küçükgergi̇n, C., Aydin, A. F."Serum expression levels of HOTAIR and miR‑646 in endometrial cancer". Oncology Letters 31.2 (2026): 90.
Chicago
Hari̇smunandar, R., Karpuzoğlu, H., Mi̇nareci̇, Y., Sözen, H., Topuz, S., Küçükgergi̇n, C., Aydin, A. F."Serum expression levels of HOTAIR and miR‑646 in endometrial cancer". Oncology Letters 31, no. 2 (2026): 90. https://doi.org/10.3892/ol.2025.15443
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