Senescence-Related Transcriptomic Analysis and Functional Characterization of ANGPTL4 in Lung Adenocarcinoma
- 1Chest Hospital, Tianjin University, Tianjin 300072, China
- 2Tianjin Institute of Cardiovascular Disease, Tianjin Chest Hospital, Tianjin 300222, China
- 3Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin 300222, China
Abstract
Background: Cellular senescence and the senescence-associated secretory phenotype (SASP) can alter communication between tumor cells and the surrounding microenvironment, but the extracellular mediators involved in this process remain poorly defined in lung adenocarcinoma (LUAD). Methods: Bulk transcriptomic analysis was used to characterize senescence-related transcriptional alterations and construct a prognostic signature. ANGPTL4 expression was evaluated in public datasets and clinical samples. Single-cell RNA-sequencing analysis was then performed to map senescence-associated gene-set scores across LUAD cell populations and to examine the cell–cell communication. ANGPTL4 depletion and overexpression were used to assess its effects on LUAD-cell proliferation, migration, and SA-β-gal positivity, while a subcutaneous xenograft model was used to examine tumor growth in vivo. Conditioned-medium and indirect co-culture experiments were performed to assess the effects of ANGPTL4-overexpressing LUAD cells on THP-1-derived macrophage inflammatory responses, and MCC950 was used to evaluate the contribution of NLRP3-associated signaling. Results: Senescence-related transcriptional alterations in LUAD were enriched in inflammatory and immune-related pathways. ANGPTL4 was included in a five-gene prognostic model and selected for functional investigation because it encodes a secreted protein. We found that ANGPTL4 protein levels were increased in LUAD tissues. Single-cell analysis showed relatively high senescence-associated gene-set scores in macrophage-enriched populations, together with stronger cell–cell communication in the higher-score group. ANGPTL4 depletion reduced LUAD-cell migration and SA-β-gal positivity, while its overexpression had the opposite effects and resulted in larger xenograft tumors. Conditioned medium and indirect co-culture experiments showed that ANGPTL4-overexpressing LUAD cells induced inflammatory changes in THP-1-derived macrophages, accompanied by increased NLRP3-associated markers and IL-1β secretion. These changes were partly attenuated by MCC950. Conclusions: These findings suggest that ANGPTL4 is associated with tumor cell–macrophage crosstalk in LUAD and may correlate with senescence-related transcriptional signatures, while the specific biological role of ANGPTL4 remains to be further characterized.
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BibTeX
@article{shi2026senescencerelated,
title = {{Senescence-Related Transcriptomic Analysis and Functional Characterization of ANGPTL4 in Lung Adenocarcinoma}},
author = {Ying Shi and Han Zhang and Yuhang Jiang and Xin Li and Daqiang Sun},
journal = {Cancers},
year = {2026},
month = nov,
doi = {10.3390/cancers18213571},
url = {https://www.mdpi.com/2072-6694/18/21/3571},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Senescence-Related Transcriptomic Analysis and Functional Characterization of ANGPTL4 in Lung Adenocarcinoma
AU - Ying Shi
AU - Han Zhang
AU - Yuhang Jiang
AU - Xin Li
AU - Daqiang Sun
PY - 2026
DA - 2026/11/06
JO - Cancers
DO - 10.3390/cancers18213571
UR - https://www.mdpi.com/2072-6694/18/21/3571
AB - Background: Cellular senescence and the senescence-associated secretory phenotype (SASP) can alter communication between tumor cells and the surrounding microenvironment, but the extracellular mediators involved in this process remain poorly defined in lung adenocarcinoma (LUAD). Methods: Bulk transcriptomic analysis was used to characterize senescence-related transcriptional alterations and construct a prognostic signature. ANGPTL4 expression was evaluated in public datasets and clinical samples. Single-cell RNA-sequencing analysis was then performed to map senescence-associated gene-set scores across LUAD cell populations and to examine the cell–cell communication. ANGPTL4 depletion and overexpression were used to assess its effects on LUAD-cell proliferation, migration, and SA-β-gal positivity, while a subcutaneous xenograft model was used to examine tumor growth in vivo. Conditioned-medium and indirect co-culture experiments were performed to assess the effects of ANGPTL4-overexpressing LUAD cells on THP-1-derived macrophage inflammatory responses, and MCC950 was used to evaluate the contribution of NLRP3-associated signaling. Results: Senescence-related transcriptional alterations in LUAD were enriched in inflammatory and immune-related pathways. ANGPTL4 was included in a five-gene prognostic model and selected for functional investigation because it encodes a secreted protein. We found that ANGPTL4 protein levels were increased in LUAD tissues. Single-cell analysis showed relatively high senescence-associated gene-set scores in macrophage-enriched populations, together with stronger cell–cell communication in the higher-score group. ANGPTL4 depletion reduced LUAD-cell migration and SA-β-gal positivity, while its overexpression had the opposite effects and resulted in larger xenograft tumors. Conditioned medium and indirect co-culture experiments showed that ANGPTL4-overexpressing LUAD cells induced inflammatory changes in THP-1-derived macrophages, accompanied by increased NLRP3-associated markers and IL-1β secretion. These changes were partly attenuated by MCC950. Conclusions: These findings suggest that ANGPTL4 is associated with tumor cell–macrophage crosstalk in LUAD and may correlate with senescence-related transcriptional signatures, while the specific biological role of ANGPTL4 remains to be further characterized.
SN - 2072-6694
ER -