Research Paper Volume 16, Issue 6 pp 5471—5500
Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer
- 1 Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
- 2 The First Affiliated Hospital of Dalian Medical University, Dalian, China
- 3 Department of Breast and Thyroid Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
- 4 Key Laboratory of Molecular Pathology in Tumors of Guangxi, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
Received: October 26, 2023 Accepted: February 8, 2024 Published: March 18, 2024
https://doi.org/10.18632/aging.205658How to Cite
Copyright: © 2024 Qiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Parthanatos is a novel programmatic form of cell death based on DNA damage and PARP-1 dependency. Nevertheless, its specific role in the context of gastric cancer (GC) remains uncertain.
Methods: In this study, we integrated multi-omics algorithms to investigate the molecular characteristics of parthanatos in GC. A series of bioinformatics algorithms were utilized to explore clinical heterogeneity of GC and further predict the clinical outcomes.
Results: Firstly, we conducted a comprehensive analysis of the omics features of parthanatos in various human tumors, including genomic mutations, transcriptome expression, and prognostic relevance. We successfully identified 7 cell types within the GC microenvironment: myeloid cell, epithelial cell, T cell, stromal cell, proliferative cell, B cell, and NK cell. When compared to adjacent non-tumor tissues, single-cell sequencing results from GC tissues revealed elevated scores for the parthanatos pathway across multiple cell types. Spatial transcriptomics, for the first time, unveiled the spatial distribution characteristics of parthanatos signaling. GC patients with different parthanatos signals often exhibited distinct immune microenvironment and metabolic reprogramming features, leading to different clinical outcomes. The integration of parthanatos signaling and clinical indicators enabled the creation of novel survival curves that accurately assess patients’ survival times and statuses.
Conclusions: In this study, the molecular characteristics of parthanatos’ unicellular and spatial transcriptomics in GC were revealed for the first time. Our model based on parthanatos signals can be used to distinguish individual heterogeneity and predict clinical outcomes in patients with GC.