Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization
Abstract Introduction Immune factors contribute to the onset of myelodysplastic syndrome (MDS). Arginine metabolism affects tumor‐associated macrophage (TAM) polarization. This study investigated the infiltration of TAMs and effect of arginine metabolism key enzymes on MDS prognosis. Methods We used...
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| Format: | Article |
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Wiley
2023-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6287 |
| _version_ | 1797361229620051968 |
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| author | Yang Ou Yan Yang Xuefeng Li Xin Zhang Lei Zhao Chenlu Yang Yu Wu |
| author_facet | Yang Ou Yan Yang Xuefeng Li Xin Zhang Lei Zhao Chenlu Yang Yu Wu |
| author_sort | Yang Ou |
| collection | DOAJ |
| description | Abstract Introduction Immune factors contribute to the onset of myelodysplastic syndrome (MDS). Arginine metabolism affects tumor‐associated macrophage (TAM) polarization. This study investigated the infiltration of TAMs and effect of arginine metabolism key enzymes on MDS prognosis. Methods We used the GEO (Gene Express Omnibus database) dataset “GSE19429” to analyze and compare metabolism‐associated pathways between MDS patients with excess blasts and those without. The markers of TAMs and arginine metabolism key enzymes, including CD68, iNOS, ARG1 and ASS1 were included in this study. A cohort of 79 patients with acute myeloid leukemia or MDS extracted from GenomicScape's online data mining platform was used to analyze the prognostic significance of the mRNA levels. Fifty‐eight patients with primary MDS admitted to Sichuan University's West China Hospital from 2013 to 2017 were evaluated for protein levels. The coexpression of CD68, iNOS, and ARG1 was investigated using an Opal polychromatic immunofluorescence kit. Results The “Arginine and proline metabolism” pathways (padjusted = 0.01) were associated with excess blasts in patients with MDS. In the mRNA expression cohort, patients with low NOS2 (or iNOS) and high ARG1, ASS1, and CD68 expression levels had worse prognosis. Patients with high CD68 (p = 0.01), high iNOS (p < 0.01), low ARG1 (p = 0.01), and negative ASS1 (p = 0.02) protein expression levels had better prognoses. iNOS and ARG1 were coexpressed with CD68 in MDS patients with or without excess blasts, respectively. Conclusions Arginine metabolism may contribute to the prognosis of patients with MDS by affecting TAM polarization. |
| first_indexed | 2024-03-08T15:50:55Z |
| format | Article |
| id | doaj.art-94d191652fb7445483ab26d6bd134b22 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T15:50:55Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-94d191652fb7445483ab26d6bd134b222024-01-09T05:41:08ZengWileyCancer Medicine2045-76342023-08-011215164441645410.1002/cam4.6287Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarizationYang Ou0Yan Yang1Xuefeng Li2Xin Zhang3Lei Zhao4Chenlu Yang5Yu Wu6Department of Hematology and Hematology Research Institute West China Hospital, Sichuan University Chengdu People's Republic of ChinaDepartment of Hematology and Hematology Research Institute West China Hospital, Sichuan University Chengdu People's Republic of ChinaDepartment of Hematology and Hematology Research Institute West China Hospital, Sichuan University Chengdu People's Republic of ChinaDepartment of Hematology and Hematology Research Institute West China Hospital, Sichuan University Chengdu People's Republic of ChinaDepartment of Hematology and Hematology Research Institute West China Hospital, Sichuan University Chengdu People's Republic of ChinaDepartment of Hematology and Hematology Research Institute West China Hospital, Sichuan University Chengdu People's Republic of ChinaDepartment of Hematology and Hematology Research Institute West China Hospital, Sichuan University Chengdu People's Republic of ChinaAbstract Introduction Immune factors contribute to the onset of myelodysplastic syndrome (MDS). Arginine metabolism affects tumor‐associated macrophage (TAM) polarization. This study investigated the infiltration of TAMs and effect of arginine metabolism key enzymes on MDS prognosis. Methods We used the GEO (Gene Express Omnibus database) dataset “GSE19429” to analyze and compare metabolism‐associated pathways between MDS patients with excess blasts and those without. The markers of TAMs and arginine metabolism key enzymes, including CD68, iNOS, ARG1 and ASS1 were included in this study. A cohort of 79 patients with acute myeloid leukemia or MDS extracted from GenomicScape's online data mining platform was used to analyze the prognostic significance of the mRNA levels. Fifty‐eight patients with primary MDS admitted to Sichuan University's West China Hospital from 2013 to 2017 were evaluated for protein levels. The coexpression of CD68, iNOS, and ARG1 was investigated using an Opal polychromatic immunofluorescence kit. Results The “Arginine and proline metabolism” pathways (padjusted = 0.01) were associated with excess blasts in patients with MDS. In the mRNA expression cohort, patients with low NOS2 (or iNOS) and high ARG1, ASS1, and CD68 expression levels had worse prognosis. Patients with high CD68 (p = 0.01), high iNOS (p < 0.01), low ARG1 (p = 0.01), and negative ASS1 (p = 0.02) protein expression levels had better prognoses. iNOS and ARG1 were coexpressed with CD68 in MDS patients with or without excess blasts, respectively. Conclusions Arginine metabolism may contribute to the prognosis of patients with MDS by affecting TAM polarization.https://doi.org/10.1002/cam4.6287arginine metabolismmyelodysplastic syndrometumor‐associated macrophage |
| spellingShingle | Yang Ou Yan Yang Xuefeng Li Xin Zhang Lei Zhao Chenlu Yang Yu Wu Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization Cancer Medicine arginine metabolism myelodysplastic syndrome tumor‐associated macrophage |
| title | Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization |
| title_full | Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization |
| title_fullStr | Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization |
| title_full_unstemmed | Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization |
| title_short | Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization |
| title_sort | arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization |
| topic | arginine metabolism myelodysplastic syndrome tumor‐associated macrophage |
| url | https://doi.org/10.1002/cam4.6287 |
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