Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion

Yoshida, Akihiko; Wakai, Susumu; Ryo, Eijitsu; Miyata, Kazuyuki; Miyazawa, Mitsuhiro; Yoshida, Kenichi; Motoi, Toru; Ogawa, Chitose; Iwata, Shintaro; Kobayashi, Eisuke; Watanabe, Shun‐ichi; Kawai, Akira; Mori, Taisuke

doi:10.1097/pas.0000000000001331

“…In addition, GO analysis has shown that the blue module is predominantly involved in chemokine-mediated and complement receptor-mediated signaling and chemokine activity. Previous researches has confirmed that the plasma, lysosomal, and lytic vacuole membranes may be potential targets for treating sarcomas [55,[57][58][59][60].…”

Section: Discussionmentioning

confidence: 94%

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

Zhu

¹

,

Hou²

2020

Preprint

0

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Background Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we aimed to characterize infiltrating immune cells and genes associated with the immunologic response to sarcomas. Method The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Gens and Genomes (KEGG) analysis were applied using the “clusterProfiler” package in R for annotation and visualization. Results Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level. Conclusion Based on the immune cell infiltration and immune microenvironment, three key genes were identified, which suggest novel molecular mechanisms of sarcoma metastasis.

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“…In addition, GO analysis has shown that the blue module is predominantly involved in chemokine-mediated and complement receptormediated signaling and chemokine activity. Previous studies have con rmed that the plasma, lysosomal, and lytic vacuole membranes may be potential targets for treating sarcomas [58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

Zhu

¹

,

Hou

²

2020

Preprint

View full text Add to dashboard Cite

Background: Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas.Method: The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization. Results: Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level.Conclusion: Based on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.

show abstract

“…In addition, GO analysis has shown that the blue module is predominantly involved in chemokine-mediated and complement receptor-mediated signaling and chemokine activity. Previous studies have con rmed that the plasma, lysosomal, and lytic vacuole membranes may be potential targets for treating sarcomas [58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

Zhu

¹

,

Hou

²

2020

Preprint

View full text Add to dashboard Cite

Background: Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas.Method: The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization. Results: Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level.Conclusion: Based on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.

show abstract

Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion

Cited by 65 publications

References 26 publications

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

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