Cell Death and Disease (Feb 2024)

Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis

  • Bo Sheng,
  • Shuya Pan,
  • Miaomiao Ye,
  • Hejing Liu,
  • Jiamin Zhang,
  • Bo Zhao,
  • Huihui Ji,
  • Xueqiong Zhu

DOI
https://doi.org/10.1038/s41419-024-06522-y
Journal volume & issue
Vol. 15, no. 2
pp. 1 – 17

Abstract

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Abstract Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell–cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.