The novel subclusters based on cancer-associated fibroblast for pancreatic adenocarcinoma

Guojie Zhao; Changjing Wang; Jian Jiao; Wei Zhang; Hongwei Yang

doi:10.3389/fonc.2022.1045477

The novel subclusters based on cancer-associated fibroblast for pancreatic adenocarcinoma

Front Oncol. 2022 Dec 5:12:1045477. doi: 10.3389/fonc.2022.1045477. eCollection 2022.

Authors

Guojie Zhao¹, Changjing Wang², Jian Jiao¹, Wei Zhang¹, Hongwei Yang³

Affiliations

¹ The Seventh Department of General Surgery, HanDan Central Hospital, Handan, Hebei, China.
² The Department of Gastrointestinal surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
³ The First Department of Oncology, HanDan Central Hospital, Handan, Hebei, China.

Abstract

Introduction: Pancreatic adenocarcinoma (PAAD) is a fatal disease characterized by promoting connective tissue proliferation in the stroma. Activated cancer-associated fibroblasts (CAFs) play a key role in fibrogenesis in PAAD. CAF-based tumor typing of PAAD has not been explored.

Methods: We extracted single-cell sequence transcriptomic data from GSE154778 and CRA001160 datasets from Gene Expression Omnibus or Tumor Immune Single-cell Hub to collect CAFs in PAAD. On the basis of Seurat packages and new algorithms in machine learning, CAF-related subtypes and their top genes for PAAD were analyzed and visualized. We used CellChat package to perform cell-cell communication analysis. In addition, we carried out functional enrichment analysis based on clusterProfiler package. Finally, we explored the prognostic and immunotherapeutic value of these CAF-related subtypes for PAAD.

Results: CAFs were divided into five new subclusters (CAF-C0, CAF-C1, CAF-C2, CAF-C3, and CAF-C4) based on their marker genes. The five CAF subclusters exhibited distinct signaling patterns, immune status, metabolism features, and enrichment pathways and validated in the pan-cancer datasets. In addition, we found that both CAF-C2 and CAF-C4 subgroups were negatively correlated with prognosis. With their top genes of each subclusters, the sub-CAF2 had significantly relations to immunotherapy response in the patients with pan-cancer and immunotherapy.

Discussion: We explored the heterogeneity of five subclusters based on CAF in signaling patterns, immune status, metabolism features, enrichment pathways, and prognosis for PAAD.

Keywords: immune features; immunotherapy; machining learning; pancreatic adenocarcinoma; prognosis; subclusters.