Suzuki Sayaka R, Kuno Akihiro, Ozaki Haruka
Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Bioinformatics Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Biochem Biophys Rep. 2021 Sep 4;28:101126. doi: 10.1016/j.bbrep.2021.101126. eCollection 2021 Dec.
Cell-to-cell interactions (CCIs) through ligand-receptor (LR) pairs in the tumor microenvironment underlie the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). However, there is scant knowledge of the association of CCIs with PDAC prognosis, which is critical to the identification of potential therapeutic candidates. Here, we sought to identify the LR pairs associated with PDAC patient prognosis by integrating survival analysis and single-cell CCI prediction. Via survival analysis using gene expression from cancer cohorts, we found 199 prognostic LR pairs. CCI prediction based on single-cell RNA-seq data revealed the enriched LR pairs associated with poor prognosis. Notably, the CCIs involved epithelial tumor cells, cancer-associated fibroblasts, and tumor-associated macrophages through integrin-related and - pairs. Finally, we determined that CCIs involving 33 poor-prognostic LR pairs were associated with tumor grade. Although the clinical implication of the set of LR pairs must be determined, our results may provide potential therapeutic targets in PDAC.
肿瘤微环境中通过配体-受体（LR）对进行的细胞间相互作用（CCI）是胰腺导管腺癌（PDAC）预后不良的基础。然而，关于CCI与PDAC预后的关联了解甚少，而这对于确定潜在的治疗候选物至关重要。在此，我们试图通过整合生存分析和单细胞CCI预测来鉴定与PDAC患者预后相关的LR对。通过使用癌症队列中的基因表达进行生存分析，我们发现了199个预后LR对。基于单细胞RNA测序数据的CCI预测揭示了与预后不良相关的富集LR对。值得注意的是，CCI通过整合素相关和其他对涉及上皮肿瘤细胞、癌症相关成纤维细胞和肿瘤相关巨噬细胞。最后，我们确定涉及33个预后不良LR对的CCI与肿瘤分级相关。尽管必须确定这组LR对的临床意义，但我们的结果可能为PDAC提供潜在的治疗靶点。
