Low-coverage whole-genome sequencing for the effective diagnosis of early endometrial cancer: A pilot study

Haifeng Qiu; Min Wang; Tingting Cao; Yun Feng; Ying Zhang; Ruixia Guo

doi:10.1016/j.heliyon.2023.e19323

Low-coverage whole-genome sequencing for the effective diagnosis of early endometrial cancer: A pilot study

Heliyon. 2023 Aug 23;9(9):e19323. doi: 10.1016/j.heliyon.2023.e19323. eCollection 2023 Sep.

Authors

Haifeng Qiu^{1

2

3

4}, Min Wang¹, Tingting Cao¹, Yun Feng¹, Ying Zhang¹, Ruixia Guo^{1

2

3

4}

Affiliations

¹ Department of Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Provincial Medical Key Laboratory for Gynecologic Malignancies Prevention and Treatment, Zhengzhou, China.
³ Zhengzhou Key Laboratory for Gynecologic Malignancies Prevention and Treatment, Zhengzhou, China.
⁴ Henan Province Engineering Research Center of Fertility Preservation in Gynecologic Tumors, Zhengzhou, Henan Province, China.

Abstract

Background: Endometrial carcinoma (EC) is a disease that predominantly affects peri- and post-menopausal women and its incidence has continued to rise over recent years. Since the gold standard for EC diagnosis-hysteroscopic biopsy-is invasive, expensive, and unsuitable for wide use, there is an urgent need for a non-invasive method that exhibits both high sensitivity and high specificity. We therefore investigated the efficacy of UterCAD (the uterine exfoliated cell chromosomal aneuploidy detector) using tampon-collected specimens for the early detection of EC.

Methods: We prospectively recruited 51 patients with a history of abnormal bleeding and who planned to undergo hysteroscopic examination or hysterectomy between March 2020 and January 2021. Before executing an invasive procedure, a tampon was inserted into the patient's vagina for 6 h to collect exfoliated cells from the uterine cavity. Total DNA was extracted and low-coverage whole-genome sequencing was performed on an Illumina HiSeq X10, and we analyzed the differences in chromosomal status between women with EC and those bearing benign lesions using UterCAD.

Results: Thirty EC patients-including 26 with endometrioid carcinoma (EEC) and four with uterine serous carcinoma (USC), as well as 14 benign cases-were enrolled in our final analysis. Copy-number variations (CNVs) were detected in tampon specimens collected from 26 EC patients (83.3%), including 21 with EEC (80.7%) and four with USC (100%). In the benign group, only one woman with focal atypical hyperplasia presented with a 10q chromosomal gain (P < 0.001). In the EC group, the most common CNVs were copy gains of 8q (N = 14), 2q (N = 4), and 10q (N = 3); and copy losses of 2q (N = 3) and 17p (N = 2). When we stratified by FIGO stage, the CNV rates in stages IA, IB, and II/III were 83.3% (15/18), 85.7% (6/7), and 80.0% (4/5), respectively. At the optimal cutoff (|Z| ≥ 2.3), UterCAD discriminated 83.3% of EC cases from benign cases, with a specificity of 92.9%.

Conclusions: We initially reported that UterCAD could serve as a non-invasive method for the early detection of EC, especially in the rare and aggressive USC subtype. The use of UterCAD might thus avoid unnecessary invasive procedures and thereby reduce the treatment burden on patients.

Keywords: Early detection; Endometrial cancer; Low-coverage whole-genome sequencing; Non-invasive.