ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmune landscape and therapeutic barriers in gastrointestinal cancersView all 7 articles
Integrative Pan-Cancer Analysis Reveals AARS2 as a Lactylation-Associated Biomarker and Therapeutic Target in Colon Adenocarcinoma
Provisionally accepted
- 1Lanzhou University Second Hospital, Lanzhou, China
- 2Lanzhou University First Hospital, Lanzhou, China
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Background: Colon adenocarcinoma (COAD) has a poor prognosis. Lactate accumulation in the tumor microenvironment (TME) drives lactylation, a key modification linking metabolism to immunosuppression and progression. Methods: We performed an integrative multi-omics analysis of lactylation-related genes (LRGs) in COAD and pan-cancer, using bulk/single-cell/spatial transcriptomics from public databases. Machine learning identified the pivotal LRG AARS2. Its oncogenic role was characterized via expression, prognostic, and TME analyses. Protein-level validation used the HPA database and immunohistochemistry (IHC) on clinical specimens. In vitro studies in HCT116 cells confirmed AARS2 expression and assessed its knockdown effects on lactate accumulation, global protein lactylation, and immune-related gene expression (CCL5, CXCL10, IFNB1). Results: AARS2 was upregulated in COAD and other cancers, with high expression correlating with worse outcomes. Single-cell/spatial analyses showed its enrichment in malignant cells and an immunosuppressive TME. Functional analyses linked it to EMT and hypoxia. IHC confirmed higher AARS2 protein in tumors, alongside elevated cGAS. In vitro, AARS2 silencing reduced extracellular lactate and global protein lactylation, while upregulating cGAS-STING pathway genes. Conclusion: AARS2 correlates with lactylation dynamics, metabolism, and immune modulation in COAD, suggesting a role in lactylation-associated cGAS-STING regulation. These findings warrant further mechanistic investigation.
Keywords: AARS2 gene, colon adenocarcinoma (COAD), Lactylation (Kla), Pan-cancer analysis, prognostic biomarker, Tumor microenvironment - TME
Received: 26 Oct 2025; Accepted: 11 Feb 2026.
Copyright: © 2026 Zou, Ding, Yu, Pan, Wu, Song, Wu and Pan. 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:
Shaobo Wu
Jiebin Pan
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