HLA-DPA1 overexpression inhibits cancer progression, reduces resistance to cisplatin, and correlates with increased immune infiltration in lung adenocarcinoma.

Abstract

PURPOSE:

Human Leukocyte Antigen-DP alpha 1 (HLA-DPA1) is a critical gene in antigen-presenting cells and plays a significant role in immune regulation. The objective of this study was to comprehensively analyze the roles of HLA-DPA1 and its association with lung adenocarcinoma (LUAD).

METHODS:

We utilized bioinformatics and conducted a meta-analysis to examine the roles of HLA-DPA1 expression on the progression and immunity of LUAD. We also performed CCK-8, wound healing, and Transwell assays to validate the functions of HLA-DPA1 in LUAD.

RESULTS:

HLA-DPA1 expression is downregulated in LUAD tissues and is associated with gender, race, age, smoking history, clinical stage, histological type, lymph node metastasis, and prognosis of patients with LUAD. HLA-DPA1 is involved in immune responses, leukocyte cell-cell adhesion, and antigen processing and presentation. Overexpression of HLA-DPA1 inhibits cancer cell proliferation, migration, and invasion while promoting cell sensitivity to cisplatin in A549 and A549/DDP cells. Additionally, overexpression of HLA-DPA1 correlates with tumor purity, stromal, immune, and ESTIMATE scores, the abundance of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils), and immune cell markers (programmed cell death 1, cytotoxic T-lymphocyte-associated protein 4, and cluster of differentiation 8A).

CONCLUSIONS:

Decreased HLA-DPA1 expression is associated with poor prognosis and immune infiltration in LUAD while HLA-DPA1 overexpression inhibits cancer cell proliferation and progression. Therefore, HLA-DPA1 shows potential as a prognostic biomarker and a therapeutic target for LUAD.

• Authors: Ke Shi, Qian-Yun Li, Yun-Qiang Zhang, Huan Huang, Dong-Xiao Ding, Wei-Min Luo, Jun Zhang, Qiang Guo
• Journal: Aging (Aging (Albany NY)) Vol. 15 Issue 20 Pg. 11067-11091 (10 27 2023) ISSN: 1945-4589 [Electronic] United States
• PMID: 37899135 (Publication Type: Meta-Analysis, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cisplatin
• HLA-DPA1 antigen

Topics

• Humans
• Cisplatin (pharmacology, therapeutic use)
• CD8-Positive T-Lymphocytes
• Adenocarcinoma of Lung (drug therapy, genetics)
• Lung Neoplasms (drug therapy, genetics)
• Prognosis