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. 2024 Aug 13;24(4):136.
doi: 10.1007/s10142-024-01416-w.

Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers

Wantao Wu #  1 , Gang Peng #  2   3 , Kaiyue Wang  2   3 , Yijian Yang  2   3 , Zhikun Liu  2   3 , Gelei Xiao  4   5
Affiliations

Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers

Wantao Wu et al. Funct Integr Genomics. .

Erratum in

Abstract

Protein disulfide isomerase A3 (PDIA3) is an endoplasmic reticulum (ER) protein. It has different functions including glycoprotein folding in the ER. The unfavorable prognosis of cancer patients was related to the abnormal PDIA3 expression level. However, it is unclear how PDIA3 correlates with the malignant characteristics of different tumors and its impact on tumor immunity. Pan-cancer data were downloaded from several databases for large-scale bioinformatics analysis. The immunological functions of PDIA3 were systematically explored at the single-cell sequencing level, including cell communication, cell metabolism, cell evolution and epigenetic modification. We performed immunofluorescence staining to visualize PDIA3 expression and infiltration of macrophages in pan-cancer samples. Further, we performed a loss-of-function assay of PDIA3 in vitro. The CCK8 assay, clone formation assay, and transwell assay were performed. M2 macrophages were co-cultured with different cell lines before the transwell assay was performed. The immunofluorescence staining of pan-cancer samples presented a higher expression of PDIA3 than those of the paired normal tissues. According to single-cell sequencing analysis, expression of PDIA3 was closely associated with cell communication, cell metabolism, cell evolution and epigenetic modification. The knockdown of PDIA3 in tumor cells inhibited cell proliferation and invasion, and restrained cocultured M2 macrophage migration. Furthermore, PDIA3 displayed predictive value in immunotherapy response in human cancer cohorts, indicating a potential therapeutic target. Our study showed that PDIA3 was associated with tumor malignant characteristics and could mediate the migration of M2 macrophages in various tumor types. PDIA3 could be a promising target to achieve tumor control and improve the immune response on a pan-cancer scale.

Keywords: Immunotherapy; Macrophage; Pan-cancer analysis; Protein disulfide isomerase A3; Single-cell RNA sequencing.

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References

    1. Boutilier AJ, Elsawa SF (2021) Macrophage Polarization States in the Tumor Microenvironment. Int J Mol Sci 22(13):6995 - PubMed - PMC - DOI
    1. Butler A, Hoffman P, Smibert P, Papalexi E, Satija R (2018) Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol 36(5):411–420 - PubMed - PMC - DOI
    1. Cao J, Spielmann M, Qiu X, Huang X, Ibrahim DM, Hill AJ et al (2019) The single-cell transcriptional landscape of mammalian organogenesis. Nature 566(7745):496–502 - PubMed - PMC - DOI
    1. Chen YC, Sahoo S, Brien R, Jung S, Humphries B, Lee W et al (2019) Single-cell RNA-sequencing of migratory breast cancer cells: discovering genes associated with cancer metastasis. Analyst 144(24):7296–7309 - PubMed - PMC - DOI
    1. Chen Y, He J, Chen R, Wang Z, Dai Z, Liang X et al (2022) Pan-cancer analysis of the immunological role of PDIA5: A potential target for immunotherapy. Front Immunol 13:881722 - PubMed - PMC - DOI

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