Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma

Abstract Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical...

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Main Authors: Jason C. Klein, Lei Wang, Douglas Strand, Chewlan Lastufka, Gregory A. Hosler, Gary C. Hon
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Molecular Cancer
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Online Access:https://doi.org/10.1186/s12943-024-02168-8
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author Jason C. Klein
Lei Wang
Douglas Strand
Chewlan Lastufka
Gregory A. Hosler
Gary C. Hon
author_facet Jason C. Klein
Lei Wang
Douglas Strand
Chewlan Lastufka
Gregory A. Hosler
Gary C. Hon
author_sort Jason C. Klein
collection DOAJ
description Abstract Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
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institution Kabale University
issn 1476-4598
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series Molecular Cancer
spelling doaj-art-8e5780871a3c4ef2a2a8af13c6227cf82024-11-17T12:13:15ZengBMCMolecular Cancer1476-45982024-11-012311610.1186/s12943-024-02168-8Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcomaJason C. Klein0Lei Wang1Douglas Strand2Chewlan Lastufka3Gregory A. Hosler4Gary C. Hon5Department of Medicine, Memorial Sloan Kettering Cancer CenterCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical CenterDepartment of Urology, University of Texas Southwestern Medical CenterProPath/Sonic HealthcareDepartment of Dermatology, University of Texas Southwestern Medical CenterCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical CenterAbstract Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.https://doi.org/10.1186/s12943-024-02168-8SarcomaPrognosisBiomarkerSingle-cell transcriptomicsSpatial transcriptomicsCollagen
spellingShingle Jason C. Klein
Lei Wang
Douglas Strand
Chewlan Lastufka
Gregory A. Hosler
Gary C. Hon
Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
Molecular Cancer
Sarcoma
Prognosis
Biomarker
Single-cell transcriptomics
Spatial transcriptomics
Collagen
title Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
title_full Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
title_fullStr Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
title_full_unstemmed Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
title_short Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
title_sort single cell and spatial transcriptomics identify col6a3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
topic Sarcoma
Prognosis
Biomarker
Single-cell transcriptomics
Spatial transcriptomics
Collagen
url https://doi.org/10.1186/s12943-024-02168-8
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