Single-cell RNA sequencing revealed subclonal heterogeneity and gene signatures of gemcitabine sensitivity in pancreatic cancer.

ABSTRACT: Introduction: Resistance to gemcitabine is common and critically limits its therapeutic efficacy in pancreatic ductal adenocarcinoma (PDAC). Methods: We constructed 17 patient-derived xenograft (PDX) models from PDAC patient samples and identified the most notable responder to gemcitabine by screening the PDX sets in vivo. To analyze tumor evolution and microenvironmental changes pre- and post-chemotherapy, single-cell RNA sequencing (scRNA-seq) was performed. Results: ScRNA-seq revealed that gemcitabine promoted the expansion of subclones associated with drug resistance and recruited macrophages related to tumor progression and metastasis. We further investigated the particular drug-resistant subclone and established a gemcitabine sensitivity gene panel (GSGP)

SUBMITTER: Hou Z 

PROVIDER: S-EPMC10267405 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature