Study of LY9 as a potential biomarker for prognosis and prediction of immunotherapy efficacy in lung adenocarcinoma

Sep 21, 2026

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The study evaluates lymphocyte antigen 9 (LY9) as a prognostic indicator and predictor of immunotherapy response in lung adenocarcinoma (LUAD). Pan-cancer expression and prognostic analyses are combined with TIMER/CIBERSORT immune infiltration correlations and GEPIA immune checkpoint associations, and a potential ceRNA network for LY9 is constructed. Gene Set Enrichment Analysis identifies LY9-related immune pathways, while GEO mRNA differential expression is validated by qRT-PCR and immune marker correlations. Protein validation includes WB, and IHC reports no detectable tumor LY9 protein expression.

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Submitted 13 April 2023 Accepted 4 July 2024 Published 23 August 2024 Corresponding author Shikang Li, [shikangli@hotmail.com](shikangli@hotmail.com)[ ](shikangli@hotmail.com)Academic editor Abhishek Tyagi Additional Information and Declarations can be found on page 19 DOI 10.7717/peerj.17816 Copyright 2024 Deng et al. Distributed under Creative Commons CC-BY-NC 4.0 OPEN ACCESS Study of LY9 as a potential biomarker for prognosis and prediction of immunotherapy efficacy in lung adenocarcinoma Kun Deng1 , Liqiang Yuan2 , Zhanyu Xu3 , Fanglu Qin4 , Zhiwen Zheng3 , Liuliu Huang3 , Wei Jiang3 , Junqi Qin3 , Yu Sun3 , Tiaozhan Zheng3 , Xinhuai Ou3 , Liping Zheng5 and Shikang Li3 1 Department of Thoracic and Cardiovascular Surgery, The Second People's Hospital of Neijiang, Neijiang, Sichuan, China 2 Department of Thoracic and Cardiovascular Surgery, People's Hospital of Deyang, Deyang, Sichuan, China 3 Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China 4 Department of Scientific Research, The First Affiliated Hospital of Guangxi Medical University, Nanning, China 5 Catheterization Laboratory of Cardiovascular Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China ABSTRACT Background. Lymphocyte antigen 9 (LY9) participates in the development of several tumors and diseases but has not been reported yet in lung adenocarcinoma (LUAD) . Methods. First, we analyzed the expression and prognostic value of LY9 in pancancer, including LUAD. Additionally, we conducted a correlation analysis of LY9 expression in LUAD with immune cell infiltration using the TIMER database and the CIBERSORT algorithm, and with immune checkpoints using the GEPIA database. Also, we constructed a potential ceRNA network for LY9 . Furthermore, we explored LY9-related pathways by Gene Set Enrichment Analysis (GSEA) . Finally, validation of differential expression at the mRNA level was obtained from the GEO database. We collected LUAD tissues for Quantitative Real-time PCR (qRT-PCR) to verify the expression of LY9, CD8, and CD4 and calculated the correlation between them. We also conducted immunohistochemistry (IHC) to verify the protein expression ofLY9 . Results. Results showed that LY9 was highly expressed in various tumors, including LUAD. Besides, patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations. The expression of LY9 in LUAD strongly and positively correlates with multiple immune cell infiltration and immune checkpoints. The functional enrichment analysis indicated that LY9 was involved in multiple immune-related pathways and non-small cell lung cancer. Moreover, a ceRNA regulatory network of LINC00943-hsa-miR-141-3p-LY9 might be involved. Finally, GSE68465 dataset confirmed differential expression ofLY9 mRNA levels in LUAD and the qRT-PCR results verified LY9 had a strong and positive correlation with CD4 and CD8 T cells. Unfortunately, IHC did not detect the expression of LY9 protein level in tumor tissues and WB experiments validated the protein expression of LY9 in the OCI-AML-2 cell line. Conclusions. Therefore, we hypothesized that LY9 could serve as a potential, novel prognostic biomarker for LUAD and could predict immunotherapy efficacy at themRNA level. How to cite this article Deng K, Yuan L, Xu Z, Qin F, Zheng Z, Huang L, Jiang W, Qin J, Sun Y, Zheng T, Ou X, Zheng L, Li S. 2024. Study ofLY9 as a potential biomarker for prognosis and prediction of immunotherapy efficacy in lung adenocarcinoma. PeerJ 12:e17816 [http://doi.org/10.7717/peerj.17816](http://doi.org/10.7717/peerj.17816) Subjects Bioinformatics, Immunology, Oncology Keywords LY9, Lung adenocarcinoma, Prognosis, Immune cell infiltration, Immune checkpoints INTRODUCTION Lung adenocarcinoma (LUAD) accounts for approximately 40% of non

FAQs

What role does LY9 play in the study of lung adenocarcinoma?

LY9 is investigated as a potential prognostic biomarker in LUAD and as a predictor of immunotherapy efficacy, focusing on its links to immune infiltration and immune checkpoints.

How was LY9’s association with immune infiltration and immune checkpoints assessed?

Immune cell infiltration correlations were analyzed using the TIMER database and the CIBERSORT algorithm, and immune checkpoint associations were assessed using the GEPIA database.

What experimental methods validated LY9 expression in LUAD samples?

The study validated LY9 differential expression at the mRNA level using GEO and qRT-PCR, and evaluated protein expression with immunohistochemistry (IHC) and Western blot (WB), including results in the OCI-AML-2 cell line.

Sep 21, 2026

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