Multiomics analysis identifies RNASET2 as a potential candidate target associated with lung adenocarcinoma
- 1Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, China
- 2The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, China
- 3Department of Neurobiology, Harbin Medical University, China
Abstract
Objective: Lung cancer is the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma representing the predominant subtype. The increasing incidence of lung adenocarcinoma underscores the urgent need to establish novel therapeutic targets for clinical intervention.
Methods: We performed Mendelian randomization and colocalization analyses on large-scale lung adenocarcinoma genome-wide association study datasets. Bulk transcriptome and single-cell RNA sequencing were further applied to explore the function of candidate targets and related cell types.
Results: Mendelian randomization revealed that elevated RNASET2 expression causally reduced the risk of lung adenocarcinoma (odds ratio = 0.817, 95% confidence interval: 0.754–0.885, p < 0.001), whereas increased BTN3A2 expression was associated with an elevated disease risk. Colocalization analysis supported a shared causal variant between RNASET2 and lung adenocarcinoma (posterior probability of hypothesis 4 = 78.6%). Bulk transcriptome data demonstrated that RNASET2 was upregulated in tumor tissues and was associated with better prognosis. Single-cell RNA sequencing revealed that macrophages were the predominant cell type expressing RNASET2, whereas weak expression was also detected in pulmonary epithelial cells and several other cell populations. There was a trend toward reduced abundance of high RNASET2-expressing macrophage subcluster 0 in tumor tissues, whereas low RNASET2-expressing subcluster 8 tended to accumulate within tumor lesions. Enrichment analysis of their signature genes suggested opposing biological roles in lung adenocarcinoma progression, which warrants further functional verification.
Conclusions: RNASET2 is closely associated with the occurrence and prognosis of lung adenocarcinoma. Macrophage-expressed RNASET2 represent a promising candidate molecule for further therapeutic exploration.
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BibTeX
@article{shi2026multiomics,
title = {{Multiomics analysis identifies RNASET2 as a potential candidate target associated with lung adenocarcinoma}},
author = {Yue Shi and Jiankun Yang and Fangyu Cai and Jian Huang and Jianing Bi and Kun Wang and Guangyou Wang and Xianglong Kong and Yaoguo Lang and Jian Zhang and Shidong Xu and Hai Xu},
journal = {The Journal of International Medical Research},
year = {2026},
month = sep,
doi = {10.1177/03000605261488089},
url = {https://doi.org/10.1177/03000605261488089},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Multiomics analysis identifies RNASET2 as a potential candidate target associated with lung adenocarcinoma
AU - Yue Shi
AU - Jiankun Yang
AU - Fangyu Cai
AU - Jian Huang
AU - Jianing Bi
AU - Kun Wang
AU - Guangyou Wang
AU - Xianglong Kong
AU - Yaoguo Lang
AU - Jian Zhang
AU - Shidong Xu
AU - Hai Xu
PY - 2026
DA - 2026/09/23
JO - The Journal of International Medical Research
DO - 10.1177/03000605261488089
UR - https://doi.org/10.1177/03000605261488089
AB - Objective: Lung cancer is the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma representing the predominant subtype. The increasing incidence of lung adenocarcinoma underscores the urgent need to establish novel therapeutic targets for clinical intervention. Methods: We performed Mendelian randomization and colocalization analyses on large-scale lung adenocarcinoma genome-wide association study datasets. Bulk transcriptome and single-cell RNA sequencing were further applied to explore the function of candidate targets and related cell types. Results: Mendelian randomization revealed that elevated RNASET2 expression causally reduced the risk of lung adenocarcinoma (odds ratio = 0.817, 95% confidence interval: 0.754–0.885, p < 0.001), whereas increased BTN3A2 expression was associated with an elevated disease risk. Colocalization analysis supported a shared causal variant between RNASET2 and lung adenocarcinoma (posterior probability of hypothesis 4 = 78.6%). Bulk transcriptome data demonstrated that RNASET2 was upregulated in tumor tissues and was associated with better prognosis. Single-cell RNA sequencing revealed that macrophages were the predominant cell type expressing RNASET2, whereas weak expression was also detected in pulmonary epithelial cells and several other cell populations. There was a trend toward reduced abundance of high RNASET2-expressing macrophage subcluster 0 in tumor tissues, whereas low RNASET2-expressing subcluster 8 tended to accumulate within tumor lesions. Enrichment analysis of their signature genes suggested opposing biological roles in lung adenocarcinoma progression, which warrants further functional verification. Conclusions: RNASET2 is closely associated with the occurrence and prognosis of lung adenocarcinoma. Macrophage-expressed RNASET2 represent a promising candidate molecule for further therapeutic exploration.
SN - 0300-0605
SN - 1473-2300
ER -