Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2
Serine proteases has been considered to be closely associated with the inflammatory response and tumor progression. As a novel serine protease, the biological function of PRSS23 is rarely studied in cancers. In this study, the prognostic significance of PRSS23 was analyzed in two-independent gastric...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.955841/full |
| _version_ | 1811267866509443072 |
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| author | Shanshan Qin Shanshan Qin Zidi Wang Congcong Huang Congcong Huang Pan Huang Pan Huang Dandan Li Dandan Li |
| author_facet | Shanshan Qin Shanshan Qin Zidi Wang Congcong Huang Congcong Huang Pan Huang Pan Huang Dandan Li Dandan Li |
| author_sort | Shanshan Qin |
| collection | DOAJ |
| description | Serine proteases has been considered to be closely associated with the inflammatory response and tumor progression. As a novel serine protease, the biological function of PRSS23 is rarely studied in cancers. In this study, the prognostic significance of PRSS23 was analyzed in two-independent gastric cancer (GC) cohorts. PRSS23 overexpression was clinically correlated with poor prognosis and macrophage infiltration of GC patients. Loss-of-function study verified that PRSS23 plays oncogenic role in GC. RNA-seq, qRT-PCR, western blotting and ELISA assay confirmed that serine protease PRSS23 positively regulated FGF2 expression and secretion. Single-cell analysis and gene expression correlation analysis showed that PRSS23 and FGF2 were high expressed in fibroblasts, and highly co-expressed with the biomarkers of tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs) and mesenchymal cells. Functional analysis confirmed PRSS23/FGF2 was required for TAM infiltration. Rescue assay further verified that PRSS23 promotes GC progression and TAM infiltration through FGF2. Survival analysis showed that high infiltration of M1-macrophage predicted favorable prognosis, while high infiltration level of M2-macrophage predicted poor prognosis in GC. Our finding highlights that PRSS23 promotes TAM infiltration through regulating FGF2 expression and secretion, thereby resulting in a poor prognosis. |
| first_indexed | 2024-04-12T21:10:19Z |
| format | Article |
| id | doaj.art-3d9827197a68483abe5658097ae3d908 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T21:10:19Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3d9827197a68483abe5658097ae3d9082022-12-22T03:16:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.955841955841Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2Shanshan Qin0Shanshan Qin1Zidi Wang2Congcong Huang3Congcong Huang4Pan Huang5Pan Huang6Dandan Li7Dandan Li8Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, ChinaLaboratory of Tumor Biology, Academy of Bio-Medicine Research, Hubei University of Medicine, Shiyan, ChinaLaboratory of Tumor Biology, Academy of Bio-Medicine Research, Hubei University of Medicine, Shiyan, ChinaHubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, ChinaLaboratory of Tumor Biology, Academy of Bio-Medicine Research, Hubei University of Medicine, Shiyan, ChinaHubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, ChinaLaboratory of Tumor Biology, Academy of Bio-Medicine Research, Hubei University of Medicine, Shiyan, ChinaHubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, ChinaLaboratory of Tumor Biology, Academy of Bio-Medicine Research, Hubei University of Medicine, Shiyan, ChinaSerine proteases has been considered to be closely associated with the inflammatory response and tumor progression. As a novel serine protease, the biological function of PRSS23 is rarely studied in cancers. In this study, the prognostic significance of PRSS23 was analyzed in two-independent gastric cancer (GC) cohorts. PRSS23 overexpression was clinically correlated with poor prognosis and macrophage infiltration of GC patients. Loss-of-function study verified that PRSS23 plays oncogenic role in GC. RNA-seq, qRT-PCR, western blotting and ELISA assay confirmed that serine protease PRSS23 positively regulated FGF2 expression and secretion. Single-cell analysis and gene expression correlation analysis showed that PRSS23 and FGF2 were high expressed in fibroblasts, and highly co-expressed with the biomarkers of tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs) and mesenchymal cells. Functional analysis confirmed PRSS23/FGF2 was required for TAM infiltration. Rescue assay further verified that PRSS23 promotes GC progression and TAM infiltration through FGF2. Survival analysis showed that high infiltration of M1-macrophage predicted favorable prognosis, while high infiltration level of M2-macrophage predicted poor prognosis in GC. Our finding highlights that PRSS23 promotes TAM infiltration through regulating FGF2 expression and secretion, thereby resulting in a poor prognosis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.955841/fullserine protease PRSS23FGF2macrophage infiltrationTAMgastric cancer |
| spellingShingle | Shanshan Qin Shanshan Qin Zidi Wang Congcong Huang Congcong Huang Pan Huang Pan Huang Dandan Li Dandan Li Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2 Frontiers in Immunology serine protease PRSS23 FGF2 macrophage infiltration TAM gastric cancer |
| title | Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2 |
| title_full | Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2 |
| title_fullStr | Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2 |
| title_full_unstemmed | Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2 |
| title_short | Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2 |
| title_sort | serine protease prss23 drives gastric cancer by enhancing tumor associated macrophage infiltration via fgf2 |
| topic | serine protease PRSS23 FGF2 macrophage infiltration TAM gastric cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.955841/full |
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