Systematic single-cell dissecting reveals heterogeneous oncofetal reprogramming in the tumor microenvironment of gastric cancer.
Shaocong MoXin ShenYulin WangYunPeng LiuTakehito SugasawaZongCheng YangWenchao GuTakahito NakajimaPublished in: Human cell (2023)
Oncofetal reprogramming of the tumor microenvironment is clinically relevant. This study used the non-negative matrix factorial (NMF) algorithm for single-cell RNA sequencing data of gastric cancer (GC) based on embryonic stem genes. Pseudotime analysis, cell-cell interaction analysis, and SCENIC analysis revealed that cancer-associated fibroblasts (CAFs), tumor-associated endothelial cells (TECs), and tumor-associated macrophages (TAMs) have different oncofetal reprogramming that affects cell function, enhances intercellular communication, and activates multiple transcription factors in these cells. Furthermore, based on the signatures of the newly defined oncofetal cell subtypes and expression profiles of large cohorts in GC patients, we determined that GJA1 + TEC-C2, IFITM1 + CAF-C3, PODXL + TEC-C1, SFRP2 + CAF-C2, and SRSF7 + CAF-C1 are crucial prognostic factors for GC patients and predictors of immune checkpoint blockade in GC. Cell subtypes were validated by immunohistochemical methods. Our novel, profound, and systematic analysis of the oncofetal reprogramming of GC may facilitate the development of improved drugs for treating GC.
Keyphrases
- single cell
- prognostic factors
- rna seq
- high throughput
- ejection fraction
- end stage renal disease
- endothelial cells
- cell therapy
- gas chromatography
- machine learning
- transcription factor
- deep learning
- gene expression
- dna methylation
- intellectual disability
- cell proliferation
- bone marrow
- neural network
- simultaneous determination