Exploring tumor heterogeneity and drug resistance in cervical cancer through single-cell and bulk transcriptomics

Cervical cancer, as one of the most common types of malignant tumors in women, poses a significant threat to the health and survival of women worldwide. Tumor drug resistance has emerged as a critical bottleneck severely limiting the efficacy of current cervical cancer treatment strategies, making it imperative to delve deeper into the underlying mechanisms for improved therapeutic outcomes.

Spatial transcriptomics and single-cell sequencing technologies were employed. Single-cell sequencing was used to uncover the heterogeneity in cervical cancer development. Pseudotime analysis, exploration of cell communication pathways, and spatial transcriptomics were further applied to investigate the roles of relevant molecules.

This study reveals an abundance of PI3 + neoplastic (NEO) in tumors and SLC40A1 + NEO cells in HSIL samples. These cell populations may play crucial roles in the development of drug resistance, as they could potentially alter the tumor microenvironment and interfere with the efficacy of therapeutic agents. Pseudotime analysis, cell communication pathways, and spatial transcriptomics highlight the pivotal role of LGALS9 and its ligands, offering new insights for early diagnosis, molecular typing, prognosis evaluation, and personalized treatment of cervical cancer.

Our findings reveal that high expression of LGALS9 suppresses T cell function, fosters a strongly immunosuppressive tumor microenvironment, and is associated with chemotherapy resistance, ineffective immunotherapy, and poor prognosis. LGALS9 may serve as a biomarker for predicting immunotherapy response. This knowledge has the potential to facilitate early diagnosis, precise molecular typing, accurate prognosis evaluation, and the development of personalized treatment strategies that can overcome tumor drug resistance and improve patient outcomes.