Histone lysine lactylation (Kla), induced by lactate in tumor microenvironment, might be a novel therapeutic target for cancer. Lung adenocarcinoma (LUAD) was characterized by lactate accumulation in the TME. However, the role of histone Kla in lung LUAD is unclear. The RNA expression profile of LUAD was downloaded from The Cancer Genome Atlas (TCGA), and then selected differentially expressed Kla-specific genes (DEKlaGs), following building a prognostic model to predict the prognosis of patients with LUAD. On the other hand, we investigated the roles of prognostic biomarkers in the LUAD immune microenvironment, and determined its roles in the LUAD therapy response. Finally, the potential KEGG pathways influenced by histone Kla were investigated through gene set enrichment analysis (GSEA). A total of eighty-six DEKlaGs were identified with the cut-off criteria log2FC ≥ 2 and p-value<0.05. Four prognostic DEKlaGs, including C1QTNF6, HCN2, SLAMF9, and IL20RB, were enrolled in the Cox regression model. We showed that high expression of lactate production-associated genes was correlated with the expression of prognostic biomarkers. On the other hand, the activation of Kla was related to LUAD immune infiltration, and played a crucial role in LUAD drug resistance and immunotherapy resistance. Moreover, Kla was associated with the activation of MARK, NOTCH, JAK/STAT signaling pathways, and contributed to the focal adhesion of LUAD. In conclusion, C1QTNF6, HCN2, SLAMF9, and IL20RB induced by histone Kla might be crucial effective biomarkers for LUAD, suggesting that Kla was expected to be a novel therapeutic target for LUAD.
| Published in | International Journal of Clinical Oncology and Cancer Research (Volume 10, Issue 2) |
| DOI | 10.11648/j.ijcocr.20251002.14 |
| Page(s) | 67-85 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2025. Published by Science Publishing Group |
LUAD, Lactate, Kla, Histone Lactylation, Immunotherapy, Prognosis
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APA Style
Zhang, Y., Ren, J., Huang, G., Wang, R. (2025). Identification of Candidate Histone Lysine Lactylation (Kla)-associated Biomarkers in Lung Adenocarcinoma (LUAD) Via Integrated Bioinformatics Analysis. International Journal of Clinical Oncology and Cancer Research, 10(2), 67-85. https://doi.org/10.11648/j.ijcocr.20251002.14
ACS Style
Zhang, Y.; Ren, J.; Huang, G.; Wang, R. Identification of Candidate Histone Lysine Lactylation (Kla)-associated Biomarkers in Lung Adenocarcinoma (LUAD) Via Integrated Bioinformatics Analysis. Int. J. Clin. Oncol. Cancer Res. 2025, 10(2), 67-85. doi: 10.11648/j.ijcocr.20251002.14
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Download@article{10.11648/j.ijcocr.20251002.14,
author = {Yi Zhang and Jianhong Ren and Guangzhao Huang and Rurong Wang},
title = {Identification of Candidate Histone Lysine Lactylation (Kla)-associated Biomarkers in Lung Adenocarcinoma (LUAD) Via Integrated Bioinformatics Analysis
},
journal = {International Journal of Clinical Oncology and Cancer Research},
volume = {10},
number = {2},
pages = {67-85},
doi = {10.11648/j.ijcocr.20251002.14},
url = {https://doi.org/10.11648/j.ijcocr.20251002.14},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20251002.14},
abstract = {Histone lysine lactylation (Kla), induced by lactate in tumor microenvironment, might be a novel therapeutic target for cancer. Lung adenocarcinoma (LUAD) was characterized by lactate accumulation in the TME. However, the role of histone Kla in lung LUAD is unclear. The RNA expression profile of LUAD was downloaded from The Cancer Genome Atlas (TCGA), and then selected differentially expressed Kla-specific genes (DEKlaGs), following building a prognostic model to predict the prognosis of patients with LUAD. On the other hand, we investigated the roles of prognostic biomarkers in the LUAD immune microenvironment, and determined its roles in the LUAD therapy response. Finally, the potential KEGG pathways influenced by histone Kla were investigated through gene set enrichment analysis (GSEA). A total of eighty-six DEKlaGs were identified with the cut-off criteria log2FC ≥ 2 and p-value<0.05. Four prognostic DEKlaGs, including C1QTNF6, HCN2, SLAMF9, and IL20RB, were enrolled in the Cox regression model. We showed that high expression of lactate production-associated genes was correlated with the expression of prognostic biomarkers. On the other hand, the activation of Kla was related to LUAD immune infiltration, and played a crucial role in LUAD drug resistance and immunotherapy resistance. Moreover, Kla was associated with the activation of MARK, NOTCH, JAK/STAT signaling pathways, and contributed to the focal adhesion of LUAD. In conclusion, C1QTNF6, HCN2, SLAMF9, and IL20RB induced by histone Kla might be crucial effective biomarkers for LUAD, suggesting that Kla was expected to be a novel therapeutic target for LUAD.
},
year = {2025}
}
TY - JOUR T1 - Identification of Candidate Histone Lysine Lactylation (Kla)-associated Biomarkers in Lung Adenocarcinoma (LUAD) Via Integrated Bioinformatics Analysis AU - Yi Zhang AU - Jianhong Ren AU - Guangzhao Huang AU - Rurong Wang Y1 - 2025/05/19 PY - 2025 N1 - https://doi.org/10.11648/j.ijcocr.20251002.14 DO - 10.11648/j.ijcocr.20251002.14 T2 - International Journal of Clinical Oncology and Cancer Research JF - International Journal of Clinical Oncology and Cancer Research JO - International Journal of Clinical Oncology and Cancer Research SP - 67 EP - 85 PB - Science Publishing Group SN - 2578-9511 UR - https://doi.org/10.11648/j.ijcocr.20251002.14 AB - Histone lysine lactylation (Kla), induced by lactate in tumor microenvironment, might be a novel therapeutic target for cancer. Lung adenocarcinoma (LUAD) was characterized by lactate accumulation in the TME. However, the role of histone Kla in lung LUAD is unclear. The RNA expression profile of LUAD was downloaded from The Cancer Genome Atlas (TCGA), and then selected differentially expressed Kla-specific genes (DEKlaGs), following building a prognostic model to predict the prognosis of patients with LUAD. On the other hand, we investigated the roles of prognostic biomarkers in the LUAD immune microenvironment, and determined its roles in the LUAD therapy response. Finally, the potential KEGG pathways influenced by histone Kla were investigated through gene set enrichment analysis (GSEA). A total of eighty-six DEKlaGs were identified with the cut-off criteria log2FC ≥ 2 and p-value<0.05. Four prognostic DEKlaGs, including C1QTNF6, HCN2, SLAMF9, and IL20RB, were enrolled in the Cox regression model. We showed that high expression of lactate production-associated genes was correlated with the expression of prognostic biomarkers. On the other hand, the activation of Kla was related to LUAD immune infiltration, and played a crucial role in LUAD drug resistance and immunotherapy resistance. Moreover, Kla was associated with the activation of MARK, NOTCH, JAK/STAT signaling pathways, and contributed to the focal adhesion of LUAD. In conclusion, C1QTNF6, HCN2, SLAMF9, and IL20RB induced by histone Kla might be crucial effective biomarkers for LUAD, suggesting that Kla was expected to be a novel therapeutic target for LUAD. VL - 10 IS - 2 ER -
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China
Department of Anesthesiology, Chengdu Shuangliu District Maternity Child Health Care Hospital, Chengdu, China
Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Department of Anesthesiology, Cheng Du Shangjin Nanfu Hospital, Chengdu, China
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