Clinical characteristics and immunosuppressive regulatory effects of DNAJC5B in esophageal squamous cell carcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HU Junxi ¹ , LIU Qingwen ² , HOU Jiaqi ² , YOU Jie ² , TIAN Shuyu ² , KONG Hao ³ ,  WANG Xiaolin ^1,3 ,  SHU Yusheng ^1,3

1. Yangzhou University School of Medicine, Yangzhou, 225000, Jiangsu, P. R. China;
2. Dalian Medical University, Dalian 116044, Liaoning, P. R. China;
3. Northern Jiangsu People's Hospital, Yangzhou, 225000, Jiangsu, P. R. China;

Corresponding author：

WANG Xiaolin, Email: shuyusheng34@163.com; SHU Yusheng, Email: shuyusheng34@163.com

Keywords：

DNAJC5B; esophageal neoplasms; tumor immunity; prognosis; immunotherapy

DOI：

10.7507/1007-4848.202408027

Video：

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Objectvie To explore the role of DNAJC5B in immunotherapy for esophageal cancer. Methods This study utilized the ESCC dataset from the TCGA database, and selected genes associated with DNAJC5B expression through Pearson correlation analysis, followed by Gene Ontology (GO) functional enrichment analysis and KEGG pathway analysis. Additionally, single-cell RNA sequencing data was used to analyze DNAJC5B expression in different T cell subgroups. The prognostic value of DNAJC5B was evaluated using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and Cox proportional hazards model analysis. Results DNAJC5B is highly expressed in advanced esophageal cancer patients, especially in males. GO and KEGG analyses revealed a significant correlation between DNAJC5B expression and immune-related processes, such as adaptive immune response and cell surface receptor signaling pathways. Single-cell analysis indicated that DNAJC5B expression is positively correlated with immune function and primarily accumulates in CD8+ T cells. Kaplan-Meier survival curves showed that the median survival time of patients with high DNAJC5B expression was 681 days, significantly lower than the 1361 days in patients with low expression. Independent prognostic analysis revealed hazard ratios of 3.577 and 4.114 for DNAJC5B, both with P-values less than 0.05. Conclusion DNAJC5B may play a significant immunomodulatory role in esophageal cancer, particularly in regulating CD8⁺ T cell function and tumor immune escape. These findings support the potential of DNAJC5B as a biomarker for treatment and prognosis evaluation in esophageal cancer

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14.	Wang Z, Zhang C, Liu X, et al. Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma. Oncoimmunology, 2016, 5(11): e1196310.
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22.	Chang Y, Li G, Zhai Y, et al. Redox regulator GLRX is associated with tumor immunity in glioma. Front Immunol, 2020, 11: 580934.
23.	Shao J, Hou L, Liu J, et al. Indoleamine 2, 3-dioxygenase 1 inhibitor-loaded nanosheets enhance CAR-T cell function in esophageal squamous cell carcinoma. Front Immunol, 2021, 12: 661357.

1. Morgan E, Soerjomataram I, Rumgay H, et al. The Global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: New estimates from GLOBOCAN 2020. Gastroenterology, 2022, 163(3): 649-658.
2. Wang J, Zhang K, Liu T, et al. Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis. Front Oncol, 2022, 12: 974684.
3. Lerut T, Coosemans W, De Leyn P, et al. Treatment of esophageal carcinoma. Chest, 1999, 116(6 Suppl): 463S-465S.
4. Bolger JC, Donohoe CL, Lowery M, et al. Advances in the curative management of oesophageal cancer. Br J Cancer, 2022, 126(5): 706-717.
5. Keenan TE, Tolaney SM. Role of Immunotherapy in triple-negative breast cancer. J Natl Compr Canc Netw, 2020, 18(4): 479-489.
6. Weng J, Li S, Zhu Z, et al. Exploring immunotherapy in colorectal cancer. J Hematol Oncol, 2022, 15(1): 95.
7. Zheng Y, Chen Z, Han Y, et al. Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment. Nat Commun, 2020, 11(1): 6268.
8. Luo H, Lu J, Bai Y, et al. Effect of camrelizumab vs placebo added to chemotherapy on survival and progression-free survival in patients with advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st randomized clinical trial. JAMA, 2021, 326(10): 916-925.
9. Wang L, Wang X, Wu Y, et al. A novel microenvironment regulated system CAR-T (MRS. CAR-T) for immunotherapeutic treatment of esophageal squamous carcinoma. Cancer Lett, 2023, 568: 216303.
10. He S, Xu J, Liu X, et al. Advances and challenges in the treatment of esophageal cancer. Acta Pharm Sin B, 2021, 11(11): 3379-3392.
11. Shi K, Li Y, Yang L, et al. Profiling transcriptional heterogeneity of epithelium, fibroblasts, and immune cells in esophageal squamous cell carcinoma by single-cell RNA sequencing. FASEB J, 2022, 36(11): e22620.
12. Rody A, Holtrich U, Pusztai L, et al. T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers. Breast Cancer Res, 2009, 11(2): R15.
13. Tang R, Liu X, Liang C, et al. Deciphering the prognostic implications of the components and signatures in the immune microenvironment of pancreatic ductal adenocarcinoma. Front Immunol, 2021 Mar 10: 12: 648917.
14. Wang Z, Zhang C, Liu X, et al. Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma. Oncoimmunology, 2016, 5(11): e1196310.
15. Li G, Wang Z, Zhang C, et al. Molecular and clinical characterization of TIM-3 in glioma through 1, 024 samples. Oncoimmunology, 2017, 6(8): e1328339.
16. Li GZ, Zhang KN, Wang Z, et al. Siglecs, novel immunotherapy targets, potentially enhance the effectiveness of existing immune checkpoint inhibitors in glioma immunotherapy. Onco Targets Ther, 2019, 12: 10263-10273.
17. Smyth EC, Lagergren J, Fitzgerald RC, et al. Oesophageal cancer. Nat Rev Dis Primers, 2017, 3: 17048.
18. Yang YM, Hong P, Xu WW, et al. Advances in targeted therapy for esophageal cancer. Signal Transduct Target Ther, 2020, 5(1): 229.
19. Fang P, Zhou J, Liang Z, et al. Immunotherapy resistance in esophageal cancer: Possible mechanisms and clinical implications. Front Immunol, 2022, 13: 975986.
20. Tsan MF, Gao B. Heat shock proteins and immune system. J Leukoc Biol, 2009, 85(6): 905-910.
21. Kim HY, Hong S. Multi-faceted roles of DNAJB protein in cancer metastasis and clinical implications. Int J Mol Sci, 2022, 23(23): 14970.
22. Chang Y, Li G, Zhai Y, et al. Redox regulator GLRX is associated with tumor immunity in glioma. Front Immunol, 2020, 11: 580934.
23. Shao J, Hou L, Liu J, et al. Indoleamine 2, 3-dioxygenase 1 inhibitor-loaded nanosheets enhance CAR-T cell function in esophageal squamous cell carcinoma. Front Immunol, 2021, 12: 661357.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

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