Predictive and prognostic transcriptomic biomarkers in soft tissue sarcomas

Abstract

Soft tissue sarcomas (STS) are rare and heterogeneous tumours comprising over 80 different histological subtypes. Treatment options remain limited in advanced STS with high rates of recurrence following resection of localised disease. Prognostication in clinical practice relies predominantly on histological grading systems as well as sarcoma nomograms. Rapid developments in gene expression profiling technologies presented opportunities for applications in sarcoma. Molecular profiling of sarcomas has improved our understanding of the cancer biology of these rare cancers and identified potential novel therapeutic targets. In particular, transcriptomic signatures could play a role in risk classification in sarcoma to aid prognostication. Unlike other solid and haematological malignancies, transcriptomic signatures have not yet reached routine clinical use in sarcomas. Herein, we evaluate early developments in gene expression profiling in sarcomas that laid the foundations for transcriptomic signature development. We discuss the development and clinical evaluation of key transcriptomic biomarker signatures in sarcomas, including Complexity INdex in SARComas (CINSARC), Genomic Grade Index, and hypoxia-associated signatures. Prospective validation of these transcriptomic signatures is required, and prospective trials are in progress to evaluate reliability for clinical application. We anticipate that integration of these gene expression signatures alongside existing prognosticators and other Omics methodologies, including proteomics and DNA methylation analysis, could improve the identification of ‘high-risk’ patients who would benefit from more aggressive or selective treatment strategies. Moving forward, the incorporation of these transcriptomic prognostication signatures in clinical practice will undoubtedly advance precision medicine in the routine clinical management of sarcoma patients.

Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level

“…Novel circulating biomarker candidates such as tumor-derived extracellular vescicles (EVs) and circulating tumor cells (CTCs) have been studied in STS [ 173 , 174 , 175 ]. Even though data regarding the prognostic significance of CTC isolation in STS are limited, a correlation between CTC presence and disease progression has been observed [ 176 , 177 ].…”

“…Bertucci et al 2017 [ 183 ] showed that PDL1 mRNA expression is heterogenous in STS, and is an independent prognostic factor of metastatic relapse. Recently clinically evaluated transcriptomic biomarker signatures such as Complexity INdex in SARComas (CINSARC), genomic grade index and hypoxia-associated signature can be integrated with biomarkers of targeted therapy enhancing prognostication [ 173 ].…”

“…A retrospective series demonstrated that the expression of PARP1 and tumors expressing high levels had worse MFS [ 183 ]. In addition, it has been reported that PARP-1 expression complemented the prognostic value of CINSARC on 5-year metastasis free survival [ 173 ].…”

Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer

“…We also observed upregulation of the COL1A1 mRNA level in lung cancer tissues compared with normal lung tissues in the Rohrbeck Lung dataset ( Figure 2 B ). Additionally, Merry et al identified that a characteristic amplification of sequences from chromosome 17q, demarcated by the COL1A1 gene, was associated with elevated expression of the COL1A1 in dermatofibrosarcoma protuberans (DFSP) 20 . These observations suggested that the COL1A1 protein may be highly expressed in lung cancer tissues.…”

Novel Insights into the Immunotherapy of Soft Tissue Sarcomas: Do We Need a Change of Perspective?

“…Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors arising from mesenchymal tissues [1]. STSs can originate from any human body location and, with more than 80 histological subtypes of STSs, data regarding novel biomarkers of strong prognostic and therapeutic value are very limited [2,3]. The most prevalent histological subtypes of STSs include liposarcoma, undifferentiated pleomorphic sarcoma, and leiomyosarcoma [4].…”