HLA-DQA1 is a potential prognostic biomarker for lung adenocarcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHENG Bowen ^1,2 , ZHU Chaonan ^1,2 ,  ZHENG Maogen ^1,2 , LI Shijiang ^1,2

1. North China University of Science and Technology, Tangshan, 063300, Hebei, P. R. China;
2. Department of Chest Tumor, Affiliated Hospital of North China University of Science and Technology, Tangshan, 063300, Hebei, P. R. China;

Corresponding author：

ZHENG Maogen, Email: 13832976291@163.com

Keywords：

HLA-DQA1; lung adenocarcinoma; tumor immune infiltration; prognosis

DOI：

10.7507/1007-4848.202501009

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the expression of major histocompatibility complex, classⅡ, DQ alpha 1 (HLA-DQA1) in lung adenocarcinoma and its prognostic significance. Methods The prognostic significance of HLA-DQA1 in lung adenocarcinoma was determined by constructing receiver operating characteristic (ROC) curve and Kaplan-Meier curve, and functional analysis was performed using gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and gene set enrichment analysis (GSEA). The association between the level of immune cell infiltration and HLA-DQA1 expression was evaluated using CIBERSORT and Spearman correlation analysis. Clinicopathological data of patients with lung adenocarcinoma who were hospitalized for surgical treatment at the North China University of Science and Technology Affiliated Hospital from 2022 to 2023 were collected, and the relationship between HLA-DQA1 expression and clinicopathological features of lung adenocarcinoma patients was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in vitro experiments. Results A total of 30 patients were included in the study, including 17 females and 13 males, with 20 cases aged ≥60 years and 10 cases aged <60 years. Compared with normal tissue, the expression level of HLA-DQA1 in lung adenocarcinoma was significantly lower, as confirmed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry in lung adenocarcinoma and normal lung tissue. CancerSEA, GO, and KEGG analyses indicated that HLA-DQA1 was closely related to the immune infiltration of tumor cells. Drug sensitivity analysis showed that patients with high HLA-DQA1 expression may be resistant to crizotinib treatment, while they are relatively sensitive to cisplatin, paclitaxel, docetaxel, and epidermal growth factor receptor inhibitors. Conclusion HLA-DQA1 is an important prognostic marker for patients with lung adenocarcinoma.

1.	Li Y, Wu X, Yang P, et al. Machine learning for lung cancer diagnosis, treatment, and prognosis. Genom Proteomics Bioinformatics, 2022, 20(5): 850-866.
2.	Daylan AEC, Miao E, Tang K, et al. Lung cancer in never smokers: Delving into epidemiology, genomic and immune landscape, prognosis, treatment, and screening. Lung, 2023, 201(6): 521-529.
3.	Abolfathi H, Sheikhpour M, Shahraeini SS, et al. Studies in lung cancer cytokine proteomics: A review. Expert Rev Proteomics, 2021, 18(1): 49-64.
4.	Salehi-Rad R, Li R, Paul MK, et al. The biology of lung cancer: Development of more effective methods for prevention, diagnosis, and treatment. Clin Chest Med, 2020, 41(1): 25-38.
5.	Wu G, Xiao G, Yan Y, et al. Bioinformatics analysis of the clinical significance of HLA class Ⅱin breast cancer. Medicine, 2022, 101(40): e31071.
6.	Liu W, Kang ZY, Wang ZL, et al. Antibody-mediated rejection owing to donor-specific HLA-DQA1 antibodies after renal transplantation: A case report. Transplant Immunol, 2022, 73: 101607.
7.	Zhou J, Xie T, Shan H, et al. HLA-DQA1 expression is associated with prognosis and predictable with radiomics in breast cancer. Radiat Oncol, 2023, 18(1): 117.
8.	Li J, Hu H, Qin G, et al. Biomarkers of pathologic complete response to neoadjuvant immunotherapy in mismatch repair-deficient colorectal cancer. Clin Cancer Res, 2024, 30(2): 368-378.
9.	Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer. Lancet, 2021, 398(10299): 535-554.
10.	Nooreldeen R, Bach H. Current and future development in lung cancer diagnosis. Int J Mol Sci, 2021, 22(16).
11.	Liu L, Soler J, Reckamp KL, et al. Emerging targets in non-small cell lung cancer. Int J Mol Sci, 2024, 25(18).
12.	Forbes SA, Trowsdale J. The MHC quarterly report. Immunogenetics, 1999, 50(3-4): 152-159.
13.	Dawkins RL, Christiansen FT, Kay PH, et al. Disease associations with complotypes, supratypes and haplotypes. Immunol Rev, 1983, 70: 5-22.
14.	Shen FF, Pan Y, Li JZ, et al. High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China. Medicine, 2019, 98(8): e14454.
15.	Zhao Y, Wei Y, Fan L, et al. Leveraging a disulfidptosis-related signature to predict the prognosis and immunotherapy effectiveness of cutaneous melanoma based on machine learning. Mol Med, 2023, 29(1): 145.
16.	Jafari N, Khajenabi F, Masumi N, et al. Evaluation of HLA-DR and HLA-DQ expression in gastric cancer tissues. J Cancer Res Ther, 2024, 20(1): 204-210.
17.	Di Y, Wang Z, Xiao J, et al. ACSL6-activated IL-18R1-NF-κB promotes IL-18-mediated tumor immune evasion and tumor progression. Sci Adv, 2024, 10(38): eadp0719.
18.	Yi M, Li T, Niu M, et al. Targeting cytokine and chemokine signaling pathways for cancer therapy. Signal Transduct Target Ther, 2024, 9(1): 176.
19.	Khare T, Bissonnette M, Khare S. CXCL12-CXCR4/CXCR7 axis in colorectal cancer: Therapeutic target in preclinical and clinical studies. Int J Mol Sci, 2021, 22(14).
20.	Mehla K, Singh PK. Metabolic regulation of macrophage polarization in cancer. Trends Cancer, 2019, 5(12): 822-834.
21.	Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol, 2020, 15: 123-147.
22.	Zheng X, Jiang Q, Han M, et al. FBXO38 regulates macrophage polarization to control the development of cancer and colitis. Cell Mol Immunol, 2023, 20(11): 1367-1378.
23.	Gunalp S, Helvaci DG, Oner A, et al. TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content. Front Immunol, 2023, 14: 1209249.
24.	Brossart P, Wirths S, Brugger W, et al. Dendritic cells in cancer vaccines. Exp Hematol, 2001, 29(11): 1247-1255.
25.	Wu Y, Wang L, Zhang Y. Dendritic cells as vectors for immunotherapy of tumor and its application for gastric cancer therapy. Cell Mol Immunol, 2004, 1(5): 351-356.
26.	Xie Z, Niu L, Zheng G, et al. Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment. Cell Biosci, 2023, 13(1): 217.
27.	Cenci S, van Anken E, Sitia R. Proteostenosis and plasma cell pathophysiology. Curr Opin Cell Biol, 2011, 23(2): 216-222.
28.	Yeong J, Lim JCT, Lee B, et al. High densities of tumor-associated plasma cells predict improved prognosis in triple negative breast cancer. Front Immunol, 2018, 9: 1209.
29.	Sakaguchi A, Horimoto Y, Onagi H, et al. Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy. Breast Cancer Res, 2021, 23(1): 99.
30.	Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cell Mol Life Sci, 2020, 77(9): 1745-1770.
31.	Elayat G, Selim A. Angiogenesis in breast cancer: Insights and innovations. Clin Exp Med, 2024, 24(1): 178.
32.	Yang Z, Zhang X, Bai X, et al. Anti-angiogenesis in colorectal cancer therapy. Cancer Sci, 2024, 115(3): 734-751.

1. Li Y, Wu X, Yang P, et al. Machine learning for lung cancer diagnosis, treatment, and prognosis. Genom Proteomics Bioinformatics, 2022, 20(5): 850-866.
2. Daylan AEC, Miao E, Tang K, et al. Lung cancer in never smokers: Delving into epidemiology, genomic and immune landscape, prognosis, treatment, and screening. Lung, 2023, 201(6): 521-529.
3. Abolfathi H, Sheikhpour M, Shahraeini SS, et al. Studies in lung cancer cytokine proteomics: A review. Expert Rev Proteomics, 2021, 18(1): 49-64.
4. Salehi-Rad R, Li R, Paul MK, et al. The biology of lung cancer: Development of more effective methods for prevention, diagnosis, and treatment. Clin Chest Med, 2020, 41(1): 25-38.
5. Wu G, Xiao G, Yan Y, et al. Bioinformatics analysis of the clinical significance of HLA class Ⅱin breast cancer. Medicine, 2022, 101(40): e31071.
6. Liu W, Kang ZY, Wang ZL, et al. Antibody-mediated rejection owing to donor-specific HLA-DQA1 antibodies after renal transplantation: A case report. Transplant Immunol, 2022, 73: 101607.
7. Zhou J, Xie T, Shan H, et al. HLA-DQA1 expression is associated with prognosis and predictable with radiomics in breast cancer. Radiat Oncol, 2023, 18(1): 117.
8. Li J, Hu H, Qin G, et al. Biomarkers of pathologic complete response to neoadjuvant immunotherapy in mismatch repair-deficient colorectal cancer. Clin Cancer Res, 2024, 30(2): 368-378.
9. Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer. Lancet, 2021, 398(10299): 535-554.
10. Nooreldeen R, Bach H. Current and future development in lung cancer diagnosis. Int J Mol Sci, 2021, 22(16).
11. Liu L, Soler J, Reckamp KL, et al. Emerging targets in non-small cell lung cancer. Int J Mol Sci, 2024, 25(18).
12. Forbes SA, Trowsdale J. The MHC quarterly report. Immunogenetics, 1999, 50(3-4): 152-159.
13. Dawkins RL, Christiansen FT, Kay PH, et al. Disease associations with complotypes, supratypes and haplotypes. Immunol Rev, 1983, 70: 5-22.
14. Shen FF, Pan Y, Li JZ, et al. High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China. Medicine, 2019, 98(8): e14454.
15. Zhao Y, Wei Y, Fan L, et al. Leveraging a disulfidptosis-related signature to predict the prognosis and immunotherapy effectiveness of cutaneous melanoma based on machine learning. Mol Med, 2023, 29(1): 145.
16. Jafari N, Khajenabi F, Masumi N, et al. Evaluation of HLA-DR and HLA-DQ expression in gastric cancer tissues. J Cancer Res Ther, 2024, 20(1): 204-210.
17. Di Y, Wang Z, Xiao J, et al. ACSL6-activated IL-18R1-NF-κB promotes IL-18-mediated tumor immune evasion and tumor progression. Sci Adv, 2024, 10(38): eadp0719.
18. Yi M, Li T, Niu M, et al. Targeting cytokine and chemokine signaling pathways for cancer therapy. Signal Transduct Target Ther, 2024, 9(1): 176.
19. Khare T, Bissonnette M, Khare S. CXCL12-CXCR4/CXCR7 axis in colorectal cancer: Therapeutic target in preclinical and clinical studies. Int J Mol Sci, 2021, 22(14).
20. Mehla K, Singh PK. Metabolic regulation of macrophage polarization in cancer. Trends Cancer, 2019, 5(12): 822-834.
21. Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol, 2020, 15: 123-147.
22. Zheng X, Jiang Q, Han M, et al. FBXO38 regulates macrophage polarization to control the development of cancer and colitis. Cell Mol Immunol, 2023, 20(11): 1367-1378.
23. Gunalp S, Helvaci DG, Oner A, et al. TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content. Front Immunol, 2023, 14: 1209249.
24. Brossart P, Wirths S, Brugger W, et al. Dendritic cells in cancer vaccines. Exp Hematol, 2001, 29(11): 1247-1255.
25. Wu Y, Wang L, Zhang Y. Dendritic cells as vectors for immunotherapy of tumor and its application for gastric cancer therapy. Cell Mol Immunol, 2004, 1(5): 351-356.
26. Xie Z, Niu L, Zheng G, et al. Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment. Cell Biosci, 2023, 13(1): 217.
27. Cenci S, van Anken E, Sitia R. Proteostenosis and plasma cell pathophysiology. Curr Opin Cell Biol, 2011, 23(2): 216-222.
28. Yeong J, Lim JCT, Lee B, et al. High densities of tumor-associated plasma cells predict improved prognosis in triple negative breast cancer. Front Immunol, 2018, 9: 1209.
29. Sakaguchi A, Horimoto Y, Onagi H, et al. Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy. Breast Cancer Res, 2021, 23(1): 99.
30. Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cell Mol Life Sci, 2020, 77(9): 1745-1770.
31. Elayat G, Selim A. Angiogenesis in breast cancer: Insights and innovations. Clin Exp Med, 2024, 24(1): 178.
32. Yang Z, Zhang X, Bai X, et al. Anti-angiogenesis in colorectal cancer therapy. Cancer Sci, 2024, 115(3): 734-751.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesHLA-DQA1 is a potential prognostic biomarker for lung adenocarcinoma

Abstract Full text Figures/Tables Video References Cited by

Format

Content