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Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma.

ABSTRACT: 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 ANXA1-FPR 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.

SUBMITTER: Suzuki SR

PROVIDER: S-EPMC8426203 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma.

Suzuki Sayaka R SR Kuno Akihiro A Ozaki Haruka H

Biochemistry and biophysics reports 20210904

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 usin ...[more]

PMID: 34522794

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Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) leads to the majority of cancer-related deaths due to its morbidity with similar mortality. Lack of effective prognostic biomarkers are the main reason for belated post-operative intervention of recurrence which causes high mortality. Numerous systematic reviews and meta-analyses have explored the prognostic value of biomarkers in PDAC so far. In this article, we performed an umbrella review analyzing these studies to provide an overview of associations between prognostic biomarkers and PDAC survival outcome and synthesized these results to guide better clinical practice. Methods: Systematic reviews and meta-analyses investigating the associations between PDAC survival outcomes and prognostic biomarkers were acquired via the PubMed and Embase databases from inception till February 1, 2020. Associations supported by nominally statistically significant results were classified into strong, highly suggestive, suggestive, and weak based on several critical factors such as the statistical significance of summary estimates, the number of events, the estimate of the largest study included, interstudy heterogeneity, small-study effects, 95% predictive interval (PI), excess significance bias, and the results of credibility ceiling sensitivity analyses. Results: We included 41 meta-analyses containing 63 associations between PDAC survival outcomes and prognostic biomarkers. Although, none was supported by strong evidence among these associations, an association between C-reactive protein to albumin ratio (CAR) and PDAC overall survival (OS) and an association between neutrophil-lymphocyte ratio (NLR) and PDAC OS were supported by highly suggestive evidence. Otherwise, the association between lactate dehydrogenase (LDH) and PDAC OS was supported by suggestive evidence. The remaining 60 associations were supported by weak or not suggestive evidence. Conclusion: Associations between CAR or NLR and PDAC OS were supported by highly suggestive evidence. And the association between LDH and PDAC OS was supported by suggestive evidence. Although the methodological quality of the included systematic reviews and meta-analyses which were evaluated by AMSTAR2.0 is generally poor, the identification of the relatively robust prognostic biomarkers of PDAC may guide better post-operative intervention and follow-up to prolong patients' survival.

Dataset Information

Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma.

Publications

Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma.

Similar Datasets

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