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Systematic single-cell dissecting reveals heterogeneous oncofetal reprogramming in the tumor microenvironment of gastric cancer

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A Correction to this article was published on 16 February 2023

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Abstract

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.

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(source HPA ID: GCAB010753. Patient ID: 2066, male, age 76). Panel2: IFITM1 + fibroblasts were marked with a black arrow. Protein was mainly expressed on cell membrane (source HPA ID: HPA004810. Patient ID: 2105, male, age 62 years). Panel3: PODXL + endothelial cells were marked with a black arrow. Protein was mainly expressed on cell membrane (source HPA ID: HPA002110. Patient ID: 2626, female, age 79 years). Panel4: SRSF7 + fibroblasts were marked with black arrows. Protein was mainly expressed in the nucleus (source HPA ID: HPA056926. Patient ID: 650, male, age 68 years)

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Data availability

The datasets generated for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and Xena GDC TCGA (https://xenabrowser.net/datapages/). IHC images can be publicly downloaded from The Human Protein Atlas (HPA) database (https://www.proteinatlas.org).

Code availability

R and other custom scripts for analyzing data are available upon request.

Change history

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Acknowledgements

We appreciate all our team members at Bioinfo_composer, the leading bioinformatics platform in China, for their selfless help.

Funding

This work was supported by JSPS KAKENHI Grant Number JP22K20814.

Author information

Author notes

  1. Shaocong Mo, Xin Shen and Yulin Wang have contributed equally to the work.

Authors and Affiliations

  1. Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Shaocong Mo & Xin Shen

  2. Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yulin Wang

  3. Department of Diagnostic and Interventional Radiology, University of Tsukuba, Ibaraki, 305-8577, Japan

    YunPeng Liu, Wenchao Gu & Takahito Nakajima

  4. Laboratory of Clinical Examination and Sports Medicine, Department of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577, Japan

    Takehito Sugasawa

  5. Department of Stomatology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, Anhui, China

    ZongCheng Yang

  6. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan

    Wenchao Gu

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Contributions

SCM and WCG analyzed the data and presented the results. WCG designed the research. XS wrote the introduction and discussion of the manuscript. YLW modified the manuscript to the submission format and made a flowchart. YPL and ZCY assisted with the literature search. TS and TN provided suggestions on data analysis. WCG and TN obtained the grant.

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Correspondence to Shaocong Mo or Wenchao Gu.

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Mo, S., Shen, X., Wang, Y. et al. Systematic single-cell dissecting reveals heterogeneous oncofetal reprogramming in the tumor microenvironment of gastric cancer. Human Cell 36, 689–701 (2023). https://doi.org/10.1007/s13577-023-00856-z

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