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03.04.2023 | Research

Integrative analyses of bulk and single-cell RNA-seq identified cancer-associated fibroblasts-related signature as a prognostic factor for immunotherapy in NSCLC

verfasst von: Shasha Wang, Guangyu Fan, Lin Li, Yajun He, Ning Lou, Tongji Xie, Liyuan Dai, Ruyun Gao, Mengwei Yang, Yuankai Shi, Xiaohong Han

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2023

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Abstract

An emerging view regarding cancer-associated fibroblast (CAF) is that it plays a critical role in tumorigenesis and immunosuppression in the tumor microenvironment (TME), but the clinical significance and biological functions of CAFs in non-small cell lung cancer (NSCLC) are still poorly explored. Here, we aimed to identify the CAF-related signature for NSCLC through integrative analyses of bulk and single-cell genomics, transcriptomics, and proteomics profiling. Using CAF marker genes identified in weighted gene co-expression network analysis (WGCNA), we constructed and validated a CAF-based risk model that stratifies patients into two prognostic groups from four independent NSCLC cohorts. The high-score group exhibits a higher abundance of CAFs, decreased immune cell infiltration, increased epithelial–mesenchymal transition (EMT), activated transforming growth factor beta (TGFβ) signaling, and a limited survival rate compared with the low-score group. Considering the immunosuppressive feature in the high-score group, we speculated an inferior clinical response for immunotherapy in these patients, and this association was successfully verified in two NSCLC cohorts treated with immune checkpoint blockades (ICBs). Furthermore, single-cell RNA sequence datasets were used to clarify the molecular mechanisms underlying the aggressive and immunosuppressive phenotype in the high-score group. We found that one of the genes in the risk model, filamin binding LIM protein 1 (FBLIM1), is mainly expressed in fibroblasts and upregulated in CAFs compared to fibroblasts from normal tissue. FBLIM1-positive CAF subtype was correlated with increased TGFβ expression, higher mesenchymal marker level, and immunosuppressive tumor microenvironment. Finally, we demonstrated that FBLIM1 might serve as a poor prognostic marker for immunotherapy in clinical samples. In conclusion, we identified a novel CAF-based classifier with prognostic value in NSCLC patients and those treated with ICBs. Single-cell transcriptome profiling uncovered FBLIM1-positive CAFs as an aggressive subtype with a high abundance of TGFβ, EMT, and an immunosuppressive phenotype in NSCLC.

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Titel: Integrative analyses of bulk and single-cell RNA-seq identified cancer-associated fibroblasts-related signature as a prognostic factor for immunotherapy in NSCLC
verfasst von: Shasha Wang
Guangyu Fan
Lin Li
Yajun He
Ning Lou
Tongji Xie
Liyuan Dai
Ruyun Gao
Mengwei Yang
Yuankai Shi
Xiaohong Han
Publikationsdatum: 03.04.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 7/2023
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-023-03428-0

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Integrative analyses of bulk and single-cell RNA-seq identified cancer-associated fibroblasts-related signature as a prognostic factor for immunotherapy in NSCLC

Abstract

Neu im Fachgebiet Onkologie

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

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Update Onkologie

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

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