Multi-Omics Analysis Identifies Phosphoglucomutase 2 as a Potential Target to Alleviate Chemoradiotherapy Resistance...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Chemoradiotherapy is the primary treatment for cervical cancer, but its effectiveness is compromised by tumor heterogeneity and resistance.
• Understanding the molecular drivers of therapeutic resistance at a single-cell level is crucial for developing new targeted therapies.
• The dynamic remodeling of the tumor microenvironment during treatment contributes to adaptive resistance in residual cancer cells.

Purpose of the Study:

• To identify key genes and cellular mechanisms driving chemoradiotherapy resistance in cervical cancer using single-cell resolution.
• To discover novel prognostic biomarkers and potential therapeutic targets for overcoming treatment resistance.
• To validate the functional role of candidate genes in chemoresistant cervical cancer cells.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was applied to paired patient samples before and after chemoradiotherapy.
• Integrated multi-omics data analysis was used to identify prognostic genes independent of heterogeneity.
• In vitro experiments on HeLa cells were conducted to assess the biological function of candidate genes, including proliferation, migration, and invasion assays.

Main Results:

• Chemoradiotherapy induced significant reprogramming of the tumor microenvironment, activating pathways like angiogenesis and epithelial-mesenchymal transition in residual cells.
• Eight prognostic genes were identified, with phosphoglucomutase 2 (PGM2) being upregulated, enriched in malignant cells, and associated with poor prognosis.
• Knockdown of PGM2 in resistant HeLa cells led to reduced proliferation, migration, and invasion, confirming its role in malignant phenotype.

Conclusions:

• PGM2 plays a role in the malignant phenotype of chemoradiotherapy-resistant cervical cancer cells.
• PGM2 is a potential candidate biomarker and therapeutic target for cervical cancer.
• Further clinical validation in larger cohorts and laboratory studies are necessary for therapeutic translation.