Cancer-associated fibroblasts are associated with poor prognosis in solid type of lung adenocarcinoma in a machine learning analysis

Abstract

Cancer-associated fibroblasts (CAFs) participate in critical processes in the tumor microenvironment, such as extracellular matrix remodeling, reciprocal signaling interactions with cancer cells and crosstalk with infiltrating inflammatory cells. However, the relationships between CAFs and survival are not well known in lung cancer. The aim of this study was to reveal the correlations of CAFs with survival rates, genetic alterations and immune activities. This study reviewed the histological features of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. We performed gene set enrichment analysis (GSEA), network-based analysis and survival analysis based on CAFs in four histological types of lung adenocarcinoma: acinar, papillary, micropapillary and solid. We found four hallmark gene sets, the epithelial-mesenchymal transition, angiogenesis, hypoxia, and inflammatory response gene sets, that were associated with the presence of CAFs. CAFs were associated with tumor proliferation, elevated memory CD4+T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, CAFs were related to blood vessel remodeling, matrix organization, negative regulation of apoptosis and transforming growth factor-β signaling. In the survival analysis of each histological type, CAFs were associated with poor prognosis in the solid type. These results may contribute to the development of therapeutic strategies against lung adenocarcinoma cases in which CAFs are present.

Multi-Omics Integrative Analysis of Lung Adenocarcinoma: An in silico Profiling for Precise Medicine

“…However, CS3 cells had higher monocytic lineage and fibroblast cell enrichment score. In lung adenocarcinoma, infiltration by B cells could independently predict favorable prognosis (47), whereas fibroblasts were reported to be associated with poor outcomes (30,48), which is consistent with the poorer prognosis in CS3.…”

Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers

“…Innate immune cells could trigger the adaptive immune responses, and understanding of cancer-intrinsic processes will supply the exploration and development of immunotherapy ( 26 , 27 ). Cancer-associated fibroblast was reported to induce cancer cell proliferation, invasion, and metastasis through various pathways ( 28 , 29 ). Moreover, Tregs that expressed the transcription factor Foxp3 could possess importance in immune homeostasis ( 26 , 30 ).…”

Integrated single-cell and spatial transcriptomic analyses unravel the heterogeneity of the prostate tumor microenvironment

“…Cancer-associated fibroblasts (CAFs) play a critical role in shaping the TME by promoting tumor proliferation and metastasis (49), enhancing angiogenesis (50), and mediating immunosuppression (51). CAFs are associated with poor prognosis in many cancer types (52)(53)(54). In prostate cancer, CAFs play a causal role in cancer development at early disease stages, contributing to therapy resistance and to metastatic progression (55).…”