Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma
Background: The alterations in metabolic profile of tumors have been identified as one of the prognostic hallmarks of cancers, including osteosarcoma. These alterations are majorly controlled by groups of metabolically active genes. However, the regulation of metabolic gene signatures in tumor micro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.814843/full |
| _version_ | 1819364672522944512 |
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| author | Zhongpei Zhu Min Zhang Weidong Wang Peng Zhang Yuqiang Wang Limin Wang |
| author_facet | Zhongpei Zhu Min Zhang Weidong Wang Peng Zhang Yuqiang Wang Limin Wang |
| author_sort | Zhongpei Zhu |
| collection | DOAJ |
| description | Background: The alterations in metabolic profile of tumors have been identified as one of the prognostic hallmarks of cancers, including osteosarcoma. These alterations are majorly controlled by groups of metabolically active genes. However, the regulation of metabolic gene signatures in tumor microenvironment of osteosarcoma has not been well explained.Objectives: Thus, we investigated the sets of previously published metabolic genes in osteosarcoma patients and normal samples.Methods: We applied computational techniques to identify metabolic genes involved in the immune function of tumor microenvironment (TME) and survival and prognosis of the osteosarcoma patients. Potential candidate gene PAICS (phosphoribosyl aminoimidazole carboxylase, phosphoribosyl aminoimidazole succino carboxamide synthetase) was chosen for further studies in osteosarcoma cell lines for its role in cell proliferation, migration and apoptosis.Results: Our analyses identified a list of metabolic genes differentially expressed in osteosarcoma tissues. Next, we scrutinized the list of genes correlated with survival and immune cells, followed by clustering osteosarcoma patients into three categories: C1, C2, and C3. These analyses led us to choose PAICS as potential candidate gene as its expression showed association with poor survival and negative correlation with the immune cells. Furthermore, we established that loss of PAICS induced apoptosis and inhibited proliferation, migration, and wound healing in HOS and MG-63 cell lines. Finally, the results were supported by constructing and validating a prediction model for prognosis of the osteosarcoma patients.Conclusion: Here, we conclude that metabolic genes specifically PAICS play an integral role in the immune cell infiltration in osteosarcoma TME, as well as cancer development and metastasis. |
| first_indexed | 2024-12-24T23:02:40Z |
| format | Article |
| id | doaj.art-6162244e348b4f179aca367ccb438f22 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-24T23:02:40Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-6162244e348b4f179aca367ccb438f222022-12-21T16:35:05ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-01-011210.3389/fgene.2021.814843814843Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in OsteosarcomaZhongpei Zhu0Min Zhang1Weidong Wang2Peng Zhang3Yuqiang Wang4Limin Wang5Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Orthopedics, Tumor Hospital of Henan Province, Zhengzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackground: The alterations in metabolic profile of tumors have been identified as one of the prognostic hallmarks of cancers, including osteosarcoma. These alterations are majorly controlled by groups of metabolically active genes. However, the regulation of metabolic gene signatures in tumor microenvironment of osteosarcoma has not been well explained.Objectives: Thus, we investigated the sets of previously published metabolic genes in osteosarcoma patients and normal samples.Methods: We applied computational techniques to identify metabolic genes involved in the immune function of tumor microenvironment (TME) and survival and prognosis of the osteosarcoma patients. Potential candidate gene PAICS (phosphoribosyl aminoimidazole carboxylase, phosphoribosyl aminoimidazole succino carboxamide synthetase) was chosen for further studies in osteosarcoma cell lines for its role in cell proliferation, migration and apoptosis.Results: Our analyses identified a list of metabolic genes differentially expressed in osteosarcoma tissues. Next, we scrutinized the list of genes correlated with survival and immune cells, followed by clustering osteosarcoma patients into three categories: C1, C2, and C3. These analyses led us to choose PAICS as potential candidate gene as its expression showed association with poor survival and negative correlation with the immune cells. Furthermore, we established that loss of PAICS induced apoptosis and inhibited proliferation, migration, and wound healing in HOS and MG-63 cell lines. Finally, the results were supported by constructing and validating a prediction model for prognosis of the osteosarcoma patients.Conclusion: Here, we conclude that metabolic genes specifically PAICS play an integral role in the immune cell infiltration in osteosarcoma TME, as well as cancer development and metastasis.https://www.frontiersin.org/articles/10.3389/fgene.2021.814843/fullosteosarcomaimmune infiltrationmetabolic genesdifferentially expressed genesPAICS |
| spellingShingle | Zhongpei Zhu Min Zhang Weidong Wang Peng Zhang Yuqiang Wang Limin Wang Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma Frontiers in Genetics osteosarcoma immune infiltration metabolic genes differentially expressed genes PAICS |
| title | Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma |
| title_full | Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma |
| title_fullStr | Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma |
| title_full_unstemmed | Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma |
| title_short | Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma |
| title_sort | global characterization of metabolic genes regulating survival and immune infiltration in osteosarcoma |
| topic | osteosarcoma immune infiltration metabolic genes differentially expressed genes PAICS |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.814843/full |
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