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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1474673
This article is part of the Research Topic Enhancing T Cell Function: Innovations in Cancer Immunotherapy View all 8 articles

Single-cell sequencing analysis reveals cancer-associated pericyte subgroup in esophageal squamous carcinoma to predict prognosis

Provisionally accepted
  • 1 Tianjin Medical University General Hospital, Tianjin, China
  • 2 Tianjia Genomes Tech Cor. Ltd., Hefei, China, Hefei, China
  • 3 Tianjin Medical University, Tianjin, China
  • 4 First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

The final, formatted version of the article will be published soon.

    The role of cancer-associated pericytes (CAPs) in tumor microenvironment (TME) suggests that they are potential targets for cancer treatment. The mechanism of CAP heterogeneity in esophageal squamous carcinoma (ESCC) remains unclear, which has limited the development of treatments for tumors through CAPs. Therefore, a comprehensive understanding of the classification, function, cellular communication and spatial distribution of CAP subpopulations in ESCC is urgently needed. Methods: This study used large-sample single-cell transcriptome sequencing (scRNA-seq) data to investigate pericytes' subpopulation characteristics, functions, upstream and downstream regulation and interactions with other components of the TME in the ESCC, and analyzed prognostically in conjunction with Bulk RNA-seq data. In addition, pericyte subpopulations were validated and their spatial distribution in the ESCC TME was observed by multiplex immunofluorescence. Drug prediction and molecular docking was further used to validate the medicinal value of drug targets. Results: CAPs in the ESCC TME were found to be highly heterogeneous, and we identified six pericyte subtypes: c1_ARHGDIB, c2_BCAM, c3_LUM, c4_SOD2, c5_TYMS, and c6_KRT17, which have commonality in a part of their functions, and each of them has a major function to play, by having different strengths of interaction with different components in the TME. In addition, we found that c4_SOD2 was negatively correlated with prognosis, conversely, c5_TYMS was positively correlated with prognosis. The drug with a better effect on c5_TYMS was docetaxel (binding energy = -8.1, -8.7 kcal/mol); raloxifene may be more effective against c4_SOD2, although raloxifene has a slightly lower binding energy to SOD2 (-6.4 kcal/mol), it has a higher binding energy to PDGFRβ (-8.1 kcal/mol).The present study identified and discovered pericyte subpopulations that were significantly associated with prognosis, which provides new biomarkers for predicting patient prognosis and adds usable targets for immunotherapy, and it is also important for gaining insights into the composition of the TME in ESCC.

    Keywords: single-cell sequencing, prognosis, Esophageal squamous carcinoma, pericyte, Cell Communication

    Received: 02 Aug 2024; Accepted: 05 Dec 2024.

    Copyright: © 2024 Xiong, Pan, Fang and Tao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ziyou Tao, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.