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Meta-Analysis
. 2023 Oct 27;15(20):11067-11091.
doi: 10.18632/aging.205082. Epub 2023 Oct 27.

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

Ke Shi  1 , Qian-Yun Li  2   3 , Yun-Qiang Zhang  1 , Huan Huang  4 , Dong-Xiao Ding  1 , Wei-Min Luo  2 , Jun Zhang  2 , Qiang Guo  2
Affiliations
Meta-Analysis

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

Ke Shi et al. Aging (Albany NY). .

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.

Keywords: The Cancer Genome Atlas; human leukocyte antigen-DP alpha 1; immune infiltration; lung adenocarcinoma; prognosis.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study.

Figures

Figure 1
Figure 1
HLA-DPA1 expression in lung adenocarcinoma tissues. (A) GSE68751; (B) GSE32863; (C) GSE10072; (D) GSE2514.
Figure 2
Figure 2
The correlation between the expression of HLA-DPA1 and demographic indicators in LUAD. (A) The expression of HLA-DPA1 in LUAD; its correlation with (B) Gender; (C) Race; (D) Age; (E) Smoking; (F) Clinical stage; (G) Tissue type; (H) Lymph node metastasis. Abbreviation: LUAD: lung adenocarcinoma; *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 3
Figure 3
The correlation between the expression of HLA-DPA1 and the diagnosis and prognosis of patients with LUAD. (A, B) Diagnostic values of HLA-DPA1 in LUAD using ROC analysis; its correlation with (C) OS; (D) DSS; (E) PFI. Abbreviations: LUAD: lung adenocarcinoma; ROC: receiver operating characteristic; OS: overall survival; DSS: disease-specific survival; PFI: progress-free interval.
Figure 4
Figure 4
The association between a decreased expression of HLA-DPA1 and poor prognosis of patients with LUAD using the LCE database. Abbreviations: LUAD: lung adenocarcinoma; LCE: Lung Cancer Explorer.
Figure 5
Figure 5
Genes positively co-expressed with HLA-DPA1 in LUAD. (A) HLA-DRA; (B) HLA-DPB1; (C) CD74; (D) HLA-DMB; (E) HLA-DRB1; (F) HLA-DOA; (G) HLA-DQA1; (H) HLA-DMA; (I) HLA-DRB5; (J) CD4; (K) HLA-DQB1; (L) ITGB2. Abbreviation: LUAD: lung adenocarcinoma.
Figure 6
Figure 6
HLA-DPA1 overexpression inhibits cancer cell proliferation and promotes cell sensitivity to cisplatin in LUAD. (A–C) A549 and A549/DDP cell assays using RT-PCR and Western blotting (D, E) Assessment of A549 and A549/DDP cell proliferation; (F) A549/DDP cell sensitivity to cisplatin. Abbreviation: LUAD: lung adenocarcinoma.
Figure 7
Figure 7
HLA-DPA1 overexpression inhibits LUAD cell migration. (A) A549; (B) A549/DDP. Abbreviation: LUAD: lung adenocarcinoma.
Figure 8
Figure 8
HLA-DPA1 overexpression inhibits LUAD cell invasion. (A) A549; (B) A549/DDP. Abbreviation: LUAD: lung adenocarcinoma.
Figure 9
Figure 9
The correlation between the HLA-DPA1 overexpression and stromal, immune, and ESTIMATE scores in LUAD. (A–C) Correlation analysis with stromal, immune, and ESTIMATE scores; (D–F) Stromal, immune, and ESTIMATE scores in high- and low-HLA-DPA1 expression groups. Abbreviation: LUAD: lung adenocarcinoma.
Figure 10
Figure 10
The correlation between the HLA-DPA1 overexpression and immune cell levels in LUAD using data from The Cancer Genome Atlas. (A) Macrophages; (B) iDC; (C) Th1 cells; (D) DC; (E) aDC; (F) TReg; (G) T cells; (H) Cytotoxic cells; (I) Mast cells. Abbreviations: LUAD: lung adenocarcinoma; DC: dendritic cells; Treg: regulatory T cells.
Figure 11
Figure 11
The association between the HLA-DPA1 overexpression and tumor purity and immune cells in LUAD using the TIMER database. Abbreviations: LUAD: lung adenocarcinoma; TIMER: Time Interval Medical Event Recorder.
Figure 12
Figure 12
The association between the HLA-DPA1 overexpression and immune cell markers in LUAD using the TIMER database. (A) T cell markers; (B) Dendritic cell markers; (C) T cell exhaustion markers. Abbreviations: DC: dendritic cells; LUAD: lung adenocarcinoma.
Figure 13
Figure 13
The association between the HLA-DPA1 overexpression and immune cell markers in LUAD using the GEPIA database. (A) CD3D; (B) CD3E; (C) CD2; (D) HLA-DPB1; (E) HLA-DQB1; (F) HLA-DRA; (G) PDCD1; (H) CTLA4; (I) LAG3. Abbreviation: LUAD: lung adenocarcinoma.
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