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.

中文翻译：

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单细胞和空间转录组学确定 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，这一系列肿瘤具有不同的病因，转移率和生存率也不同。这类多形性肉瘤中的两种基于皮肤的肿瘤，即非典型纤维黄瘤 （AFX） 和多形性真皮肉瘤 （PDS），在初始活检中难以区分，但预后差异很大。我们对 5 个 AFX 和 PDS 活检标本进行了单细胞转录组学研究，对 1 个 PDS 切除标本进行了单细胞和空间转录组学研究，以更好地表征这些肿瘤。AFX 和 PDS 之间的主要差异基因可预测人类蛋白质图谱中包含的其他 17 种癌症的总生存期。在这些基因中，COL6A3 和 BGN 分别预测 46 例和 38 例 UPS 肿瘤独立队列的总生存期和无转移生存期。COL6A3 对 UPS 患者总生存期的预测性最强，在预测 UPS 转移方面优于已建立的肉瘤预后基因组。