Systematic screening identifies a 2‐gene signature as a high‐potential prognostic marker of undifferentiated pleomorphic sarcoma/myxofibrosarcoma

Abstract

The Cancer Genome Atlas (TCGA) Research Network confirmed that undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) share a high level of genomic similarities and fall into a single spectrum of tumour. However, no molecular prognostic biomarkers have been identified in UPS/MFS. In this study, by extracting data from TCGA‐Sarcoma (SARC), we explored relapse‐related genes, their prognostic value and possible mechanisms of the dysregulations. After systematic screening, ITGA10 and PPP2R2B were included to construct a 2‐gene signature. The 2‐gene signature had an AUC value of 0.83 and had an independent prognostic value in relapse‐free survival (RFS) (HR: 2.966, 95%CI: 1.995‐4.410 P < .001), and disease‐specific survival (DSS) (HR: 2.283, 95%CI: 1.358‐3.835, P = .002), as a continuous variable. Gene‐level copy number alterations (CNAs) were irrelevant to their dysregulation. Two CpG sites (cg15585341 and cg04126335) around the promoter of ITGA10 showed strong negative correlations with ITGA10 expression (Pearson's r < −0.6). Transcript preference was observed in PPP2R2B expression. The methylation of some CpG sites in two gene body regions showed at least moderate positive correlations (Pearson's r > .4) with PPP2R2B expression. Besides, the 2‐gene signature showed a moderate negative correlation with CD4 + T cell infiltration. High‐level CD4 + T cell infiltration and neutrophil infiltration were associated with significantly better RFS. Based on these findings, we infer that the 2‐gene signature might be a potential prognostic marker in patients with UPS/MFS. Considering the potential benefits of immunotherapy for UPS/MFS patients, it is imperative to explore the predictive value of this signature in immunotherapeutic responses in the future.

Comprehensive profiling of immune-related genes in soft tissue sarcoma patients

“…We also constructed two comprehensive nomograms with satisfactory AUCs (OS: 0.832–0.926, PFS: 0.776–0.874) based on independent variables to assess the deterioration and survival of patients. To date, numerous studies have developed signatures based on sequencing data to stratify sarcoma patients, including CINSARC [ 64 ], alternative splicing events [ 65 ], relapse-related genes [ 66 ], and lncRNA [ 67 ]. However, none of them has been applied in clinical practice.…”

The Biology of Myxofibrosarcoma: State of the Art and Future Perspectives

“…Hu et al [14] evaluated 61 MFS and undifferentiated pleomorphic sarcoma (UPS). They found that increased ITGA10 and decreased PPP2R2B expression had independent prognostic value.…”

“…Ogura et al [31] observed that the average fraction of infiltrated CD8+ T cells was significantly higher in the better prognostic cluster in MFS. Hu et al [14] reported that a high level of CD4+ T-cell infiltration was associated with a significantly better relapse-free survival in UPS and MFS. They also found a moderate negative correlation between the 2-gene signature (increased ITGA10 and decreased PPP2R2B) and CD4+ T-cell infiltration.…”

A Prognostic Molecular Signature of N⁶-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database

“…Soft-tissue sarcomas are a group of heterogeneous and rare mesenchymal tumors with aggressive behavior. Tumor resection and radiotherapy are still the main treatments for non-metastatic sarcomas [ 1 ]. Although the 5-year overall survival (OS) rate is about 70% in sarcomas [ 2 ], poor prognosis is common with local recurrence [ 3 ].…”