Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 15;23(1):257.
doi: 10.1186/s12943-024-02168-8.

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

Jason C Klein  1   2 , Lei Wang  3 , Douglas Strand  4 , Chewlan Lastufka  5 , Gregory A Hosler  6   5 , Gary C Hon  7
Affiliations

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

Jason C Klein et al. Mol Cancer. .

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.

Keywords: Atypical fibroxanthoma; Biomarker; Collagen; Pleomorphic dermal sarcoma; Prognosis; Sarcoma; Single-cell transcriptomics; Spatial transcriptomics; Undifferentiated pleomorphic sarcoma.

PubMed Disclaimer

Conflict of interest statement

Declarations Ethics approval and consent to participate The UT Southwestern Human Research Protection Program (HRPP) reviewed this project and determined that it does not meet the definition of human subjects’ research under 45 CFR 46.102 and therefore does not require IRB approval or oversight. Consent for publication Not applicable. Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of scRNA-seq in AFX and PDS specimens. (A) Schematic of two PDS and three AFX tumors that were analyzed with single-cell and spatial transcriptomics. (B) UMAP of scRNA-seq of Pt 1 PDS excision specimen. Clusters are labeled by predicted cell type. (C) UMAP of scRNA-seq of the five biopsy specimens in panel A. Clusters are labeled by predicted cell type. (D) Prognostic value of the top 30 genes enriched in PDS over AFX for overall survival in 17 cancer types included in the Human Protein Atlas. The number of cancer types for which each gene has an unfavorable prognostic value is in red to the left and the number of cancer types for which each gene has a favorable prognostic value is in green to the right. (E) PDGFRA (fibroblast), PDGFRB (tumor cells), and COL6A3 (prognostic marker) expression in cells from the five biopsy specimens in panel A.
Fig. 2
Fig. 2
Prognostic value of COL6A3 in two independent cohorts of patients with UPS. (A) Cohort 1: Overall survival of 46 patients with UPS included in the Cancer Genome Atlas separated by expression of COL6A3 with log-rank p-value. (B) Cohort 2: Top row displays metastasis-free survival in 74 non-UPS sarcomas separated by CINSARC class (left) or COL6A3 expression (right). Bottom row displays metastasis-free survival for 38 UPS tumors, separated by CINSARC class (left) or COL6A3 expression (right). (C) Cohort 2: ROC curves for metastasis in 74 non-UPS sarcomas (top) or 38 UPS tumors (bottom) based on COL6A3 expression
See this image and copyright information in PMC

References

    1. Wang W-L, Torres-Cabala C, Curry JL, Ivan D, McLemore M, Tetzlaff M, et al. Metastatic atypical fibroxanthoma: a series of 11 cases including with minimal and no subcutaneous involvement. Am J Dermatopathol. 2015;37(6):455–61. - PubMed
    1. Ørholt M, Abebe K, Rasmussen LE, Aaberg FL, Lindskov LJ, Schmidt G, et al. Atypical fibroxanthoma and pleomorphic dermal sarcoma: local recurrence and metastasis in a nationwide population-based cohort of 1118 patients. J Am Acad Dermatol. 2023;89(6):1177–84. - PubMed
    1. Chibon F, Lagarde P, Salas S, Pérot G, Brouste V, Tirode F, et al. Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nat Med. 2010;16(7):781–7. - PubMed
    1. Ak M, Kahraman A, Arnold FM, Turko P, Levesque MP, Zoche M, et al. Clinicopathological and genomic profiles of atypical fibroxanthoma and pleomorphic dermal sarcoma identify overlapping signatures with a high mutational burden. Genes (Basel). 2021;12(7):974. - PMC - PubMed
    1. Griewank KG, Wiesner T, Murali R, Pischler C, Müller H, Koelsche C, et al. Atypical fibroxanthoma and pleomorphic dermal sarcoma harbor frequent NOTCH1/2 and FAT1 mutations and similar DNA copy number alteration profiles. Mod Pathol. 2018;31(3):418–28. - PMC - PubMed

MeSH terms