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Research ArticleClinical Studies

Prediction of Responsiveness to PD-L1/PD-1 Inhibitors Using miRNA Profiles Associated With PD-L1 Expression in Lung Adenocarcinoma and Squamous Cell Carcinoma

YOUNG WHA KOH, JAE-HO HAN, SEOKJIN HAAM and HYUN WOO LEE
Anticancer Research May 2024, 44 (5) 2081-2089; DOI: https://doi.org/10.21873/anticanres.17012
YOUNG WHA KOH
1Department of Pathology, Ajou University School of Medicine, Gyeonggi-do, Republic of Korea;
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  • For correspondence: youngwha9556@gmail.com
JAE-HO HAN
1Department of Pathology, Ajou University School of Medicine, Gyeonggi-do, Republic of Korea;
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SEOKJIN HAAM
2Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Gyeonggi-do, Republic of Korea
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HYUN WOO LEE
3Department of Hematology-Oncology, Ajou University School of Medicine, Gyeonggi-do, Republic of Korea
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Abstract

Background/Aim: MicroRNAs (miRNAs) regulate programmed cell death ligand 1 (PD-L1) and play a crucial role in tumor immune response. However, the relationship between miRNA expression patterns and PD-L1 remains unclear in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We investigated PD-L1-related miRNAs that can predict treatment response in patients treated with PD-L1/PD-1 inhibitors. Patients and Methods: We selected miRNAs that were correlated with PD-L1 expression within the LUAD and LUSC datasets obtained from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). We validated whether the miRNA profile could be used to predict the prognosis of patients treated with PD-L1/PD-1 inhibitors. Results: Based on four public datasets, we selected 66 and 23 miRNAs associated with PD-L1 expression in LUAD and LUSC, respectively. From the above miRNAs, we identified 5 miRNAs in LUSC and 1 miRNA in LUAD that could predict the response to PD-L1/PD-1 inhibitors in a validation set of patients treated with PD-L1/PD-1 inhibitors. In LUSC, the miRNA profile exhibited a high predictive capability for the response to PD-L1/PD-1 treatment [area under the curve (AUC)=0.963] and accurately predicted prognosis (p=0.031). In LUAD, the miRNA profile was relatively less predictive than in LUSC (AUC=0.691 and p=0.213). Additionally, we observed variations in the PD-L1-associated miRNA profiles, as well as in the associated pathways, between LUAD and LUSC. Conclusion: The PD-L1-associated miRNA profile may predict treatment response in LUSC patients treated with PD-L1/PD-1 inhibitors and help select the PD-L1/PD-1 inhibitor treatment group.

Key Words:
  • Lung squamous cell carcinoma
  • lung adenocarcinoma
  • PD-L1
  • PD-1
  • miRNA
  • Received February 11, 2024.
  • Revision received March 14, 2024.
  • Accepted March 19, 2024.
  • Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 44 (5)
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Prediction of Responsiveness to PD-L1/PD-1 Inhibitors Using miRNA Profiles Associated With PD-L1 Expression in Lung Adenocarcinoma and Squamous Cell Carcinoma
YOUNG WHA KOH, JAE-HO HAN, SEOKJIN HAAM, HYUN WOO LEE
Anticancer Research May 2024, 44 (5) 2081-2089; DOI: 10.21873/anticanres.17012

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Prediction of Responsiveness to PD-L1/PD-1 Inhibitors Using miRNA Profiles Associated With PD-L1 Expression in Lung Adenocarcinoma and Squamous Cell Carcinoma
YOUNG WHA KOH, JAE-HO HAN, SEOKJIN HAAM, HYUN WOO LEE
Anticancer Research May 2024, 44 (5) 2081-2089; DOI: 10.21873/anticanres.17012
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Keywords

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