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Risk score based on expression of five novel genes predicts survival in soft tissue sarcoma.

ABSTRACT: In this study, The Cancer Genome Atlas and Genotype-Tissue Expression databases were used to identify potential biomarkers of soft tissue sarcoma (STS) and construct a prognostic model. The model was used to calculate risk scores based on the expression of five key genes, among which MYBL2 and FBN2 were upregulated and TSPAN7, GCSH, and DDX39B were downregulated in STS patients. We also examined gene signatures associated with the key genes and evaluated the model's clinical utility. The key genes were found to be involved in the cell cycle, DNA replication, and various cancer pathways, and gene alterations were associated with a poor prognosis. According to the prognostic model, risk scores negatively correlated with infiltration of six types of immune cells. Furthermore, age, margin status, presence of metastasis, and risk score were independent prognostic factors for STS patients. A nomogram that incorporated the risk score and other independent prognostic factors accurately predicted survival in STS patients. These findings may help to improve prognostic prediction and aid in the identification of effective treatments for STS patients.

SUBMITTER: Gu HY

PROVIDER: S-EPMC7066896 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Risk score based on expression of five novel genes predicts survival in soft tissue sarcoma.

Gu Hui-Yun HY Zhang Chao C Guo Jia J Yang Min M Zhong Hou-Cheng HC Jin Wei W Liu Yang Y Gao Li-Ping LP Wei Ren-Xiong RX

Aging 20200221 4

In this study, The Cancer Genome Atlas and Genotype-Tissue Expression databases were used to identify potential biomarkers of soft tissue sarcoma (STS) and construct a prognostic model. The model was used to calculate risk scores based on the expression of five key genes, among which MYBL2 and FBN2 were upregulated and TSPAN7, GCSH, and DDX39B were downregulated in STS patients. We also examined gene signatures associated with the key genes and evaluated the model's clinical utility. The key gen ...[more]

PMID: 32084007

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Project description:Background:Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer. Methods:We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. Results:Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI?=?29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI?=?23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI?=?9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI?=?48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI?=?35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI?=?27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI?=?245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI?=?37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI?=?20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma. Conclusions:For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.

Dataset Information

Risk score based on expression of five novel genes predicts survival in soft tissue sarcoma.

Publications

Risk score based on expression of five novel genes predicts survival in soft tissue sarcoma.

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