Abstract
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.
Highlights
Osteosarcoma is a rare type of cancer that affects the individuals of all ages including children (Yang et al, 2021)
We studied the role of these genes in immune cell infiltration in osteosarcoma tumor microenvironment (TME), and a prediction model was developed to predict the overall survival (OS) and prognosis of the osteosarcoma patients
To identify the metabolic genes correlated with OS in osteosarcoma patients, we first downloaded the raw RNA-seq data of osteosarcoma patients mentioned in two different studies (Haider et al, 2016; Peng et al, 2018)
Summary
Osteosarcoma is a rare type of cancer that affects the individuals of all ages including children (Yang et al, 2021). It is noteworthy that only 15% to 20% of the patients were usually diagnosed with metastases, and the OS of these patients was reported to be extremely poor (Durnali et al, 2013; Zhang et al, 2019) Immunotherapy, such as adoptive cellular therapy, vaccination, and checkpoint inhibitors, has been considered as the effective therapies for osteosarcoma (Lettieri et al, 2016; Heymann et al, 2019). Extensive studies on the TME have shown that infiltrating immune cells play a vital role in tumor growth, recurrence, metastasis, and response to the immunotherapy (Ma et al, 2020; Zhang et al, 2020). The regulation of metabolic gene signatures in tumor microenvironment of osteosarcoma has not been well explained
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