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

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-11-15 DOI:10.1186/s12943-024-02168-8

Jason C. Klein, Lei Wang, Douglas Strand, Chewlan Lastufka, Gregory A. Hosler, Gary C. Hon

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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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单细胞和空间转录组学发现COL6A3是未分化多形性肉瘤的预后生物标志物

未分化多形性肉瘤（UPS）和相关肿瘤是最常见的软组织肉瘤类型。然而，这类肿瘤的病因不同，转移率和存活率也各异。这一类多形性肉瘤中有两种基于真皮的肿瘤，即非典型纤维黄瘤（AFX）和多形性真皮肉瘤（PDS），它们在最初的活检中很难区分，但预后却有很大差异。我们对五例 AFX 和 PDS 活检标本进行了单细胞转录组学研究，并对一例 PDS 切除标本进行了单细胞和空间转录组学研究，以更好地描述这些肿瘤的特征。AFX和PDS之间差异最大的基因可预测人类蛋白质图谱（Human Protein Atlas）中其他17种癌症的总生存率。在这些基因中，COL6A3和BGN分别预测了46个和38个UPS肿瘤独立组群的总生存率和无转移生存率。COL6A3最能预测UPS患者的总生存期，在预测UPS转移方面优于已建立的肉瘤预后基因小组。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

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