A dynamic molecular landscape in colorectal cancer progression at single-cell resolution.

BACKGROUND: Precursor lesions like polyps and adenomas in the colon commonly precede colorectal cancer (CRC), advancing through the "normal-polyp-adenoma-carcinoma" sequence towards malignancy. Yet, the cellular heterogeneity and molecular mechanisms involved in CRC development remain inadequately characterized. METHODS: To understand the molecular mechanisms driving the onset and progression of CRC, we conducted a comprehensive analysis of ten clinical colorectal samples representing sequential pathological stages using single-cell RNA sequencing (scRNA-seq). Validation was performed through immunofluorescence and immunohistochemistry analyses in a separate human colorectal tissue cohort. Additional verification was carried out using bioinformatics analyses of public TCGA and GEO datasets. RESULTS: Our comprehensive analyses not only reveal the cellular diversity and transcriptomic differences throughout disease progression but also highlight the importance of leveraging ligand-receptor gene expression to distinguish various cell subtypes. Subsequent examination and validation with a larger sample cohort uncover the specific involvement of ligand-receptor genes, transcription factors, immunoglobulin genes, and heat shock genes in regulating immune responses and microenvironment changes during colorectal tumorigenesis. CONCLUSIONS: Our extensive transcriptome dataset provides valuable insights and acts as a fundamental resource to deepen our understanding of the complex molecular landscape in CRC. This dataset facilitates improved diagnostic accuracy and the creation of more personalized therapeutic approaches.