Integração de dados de single cell RNA e transcriptoma espacial para investigação da invasão perineural e do ritmo circadiano no adenocarcinoma de pâncreas

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is recognized for its aggressiveness and unfavorable prognosis, with perineural invasion (PNI) being a significant contributor to clinical severity. The present studies explored PDAC at distinct molecular levels, utilizing single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics. The first study investigated the molecular complexities of PNI in PDAC, focusing on Pancreatic Stellate Cells (PSCs) and critical genes such as SPP1, IGFBP3, PLAU, and POSTN. We observed distinct signaling patterns in PNI-positive tumors, emphasizing the importance of PSCs and myeloid cells, and identified modules associated with fundamental cellular processes like antigen presentation and immune modulation. Spatial transcriptomics data corroborated scRNA results, demonstrating that POSTN-expressing PSCs are proximal to tumor cells and express collagen family genes. The second study examined the effects of chronic jet lag on PDAC, also using scRNA-seq in an animal model of PDAC induction. Significant alterations in cellular composition, interactions, and gene expression patterns were observed, with a notable increase in acinar and myeloid cells under chronic jet lag. We highlighted a distinct cytokine production profile in myeloid cells, particularly marked by upregulation of genes associated with chemokine receptors like Cxcl12, and identified modules enriched in macrophages under chronic jet lag, emphasizing the impact of disrupted circadian rhythms on the tumor microenvironment. Both studies underscore cellular plasticity and gene expression patterns in response to PNI and chronic jet lag, offering valuable insights into immune regulation mechanisms and potential therapeutic targets for future investigations.