Hydralazine Induced Immunologic Response by scRNA-Seq with Olink Proteomics Associated with Survival Time of pancreatic cancer
Main Article Content
Abstract
Background: Pancreatic cancer is a highly lethal cancer with no treatment options when diagnosed at an advanced stage. Hapten combined with chemotherapy drugs have been successfully injected into the tumor for local treatment of pancreatic cancer, but due to the heterogeneity of the tumor, the survival time of patients with similar stages is different.
Methods: SCNA-SEQ and Olink proteomics methods were used to observe the cell and genome changes in the survival group treated with hyrazine combined with HEIC for more than 10 months and less than 6 months. scRNA-Seq shows T cell activity of cDCs and polygene-expressed pDCs.
Results: scRNA-Seq confirmed the initiation of immune response: NaiveT and CD8Teff increased, proliferation increased, NK decreased, and ribosomal protein gene upregulated after treatment. The Neutrophils_4 gene set score of precursor cell neutrophilS_4 was higher. There was high expression of interferon-stimulating gene in neutrophils s_3, and high expression of s_3 characteristic gene set in interferon-associated neutrophils. Due to immune action, proteomic results showed that GZMB, GZMZ, IL18, CASP-8, CD8A, HO-1 and AOA genes were up-regulated by 8%. DCN, MCP-1, CX3cl1, CD40, CD27, IL33, TIE2, Gal-9, PGE, MCP-3, CD28, PD-L1, CD38, CCL3, MCP-2, MMP7, laptgf-β-1 genes were down-regulated by 18%.
Conclusions: Overall, the study showed that patients with similar stages of pancreatic cancer had an enhanced immune response after the same regimen of HEIC treatment, and found that gene expression increased by 8% and decreased by 18% in the longer survival group compared with the shorter survival group due to tumor heterogeneity.
Keywords:
Local drug delivery, Hydralazine induces immunity Immune response with local therapy, Hapten enhanc intratumoral therapy, scRNA-Seq, Olink Proteomics
Article Details
How to Cite
YU, Baofa et al.
Hydralazine Induced Immunologic Response by scRNA-Seq with Olink Proteomics Associated with Survival Time of pancreatic cancer.
Medical Research Archives, [S.l.], v. 13, n. 4, may 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6571>. Date accessed: 23 june 2025.
doi: https://doi.org/10.18103/mra.v13i4.6571.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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29. Zhou S., Lu H., Xiong M. Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis. Front Immunol. 2021 Aug 13:12:726747. doi: 10.3389/fimmu.2021.726747. eCollection 2021.
30. Chiang SK., Chen SE., Ling-Chu Chang LC. The Role of HO-1 and Its Crosstalk with Oxidative Stress in Cancer Cell Survival. Cells. 2021 Sep 13;10(9):2401. doi: 10.3390/cells10092401.
31. Guo Y., Chen T., Liang X., et al. Tumor Cell Derived Exosomal GOT1 Suppresses Tumor Cell Ferroptosis to Accelerate Pancreatic Cancer Progression by Activating Nrf2/HO-1 Axis via Upregulating CCR2 Expression. Cells. 2022 Dec 2;11(23):3893. doi: 10.3390/cells11233893.
32. Li J., Byrne KT., Yan F., et al. Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy. Immunity. 2018 Jul 17;49(1):178-193.e7. doi: 10.1016/j.immuni.2018.06.006. Epub 2018 Jun 26.
33. Bluestein BM., Morrish F., Graham DJ., et al. Analysis of the Myc-induced pancreatic β cell islet tumor microenvironment using imaging ToF-SIMS. Biointerphases. 2018 Aug 28;13(6):06D402. doi: 10.1116/1.5038574.
34. Peng J., Sun BF., Chen CY., et al. Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 2019 Sep;29(9):725-738. doi: 10.1038/s41422-019-0195-y. Epub 2019 Jul 4.