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

Cell Death Dis. 2024 Feb 12;15(2):130. doi: 10.1038/s41419-024-06522-y.

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.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Squamous Cell* / pathology
  • Cervix Uteri / pathology
  • Ecosystem
  • Female
  • Humans
  • Papillomavirus Infections* / pathology
  • Sequence Analysis, RNA
  • Tumor Microenvironment / genetics
  • Uterine Cervical Dysplasia* / diagnosis
  • Uterine Cervical Dysplasia* / pathology
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Biomarkers, Tumor