Dataset Information

GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas.

ABSTRACT:

Objective

Recent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients.

Methods

We evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases.

Result

GATA3-positive expression was significantly associated with a higher mitotic count (P < 0.0001). Disease-free survival (DFS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0104). Overall survival (OS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0006). GATA3-positive expression was significantly associated with shorter DFS in both univariate analysis (hazard ratio [HR], 2.719; P = 0.012) and multivariate analysis (HR, 2.711; P = 0.014). GATA3-positive expression was also significantly associated with worse OS in both univariate analysis (HR, 5.730; P = 0.0007) and multivariate analysis (HR, 5.789; P = 0.0008).

Conclusion

These results indicate that GATA3 is an independent prognostic factor and suggest that evaluation of GATA3 expression might enable more effective clinical follow-up using prognostic stratification of STS patients.

SUBMITTER: Haraguchi T

PROVIDER: S-EPMC4889143 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas.

Haraguchi Toshiaki T Miyoshi Hiroaki H Hiraoka Koji K Yokoyama Shintaro S Ishibashi Yukinao Y Hashiguchi Toshihiro T Matsuda Koutaro K Hamada Tetsuya T Okawa Takahiro T Shiba Naoto N Ohshima Koichi K

PloS one 20160601 6

<h4>Objective</h4>Recent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients.<h4>Methods</h4>We evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases.<h4>Result</h4>GATA3-p ...[more]

PMID: 27249072

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Project description:BackgroundSoft tissue sarcomas (STS) are heterogeneous and pro-metastatic tumors. Identification of accurate prognostic factors and novel therapeutic targets are crucial. CSPG4 is a cell surface proteoglycan with oncogenic functions. It recently emerged as a potential target for immunotherapy, including cell therapy based on CSPG4-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CSPG4-CAR.CIKs) in STS. However, expression of CSPG4 is poorly known in STS so far.MethodsWe analyzed CSPG4 gene expression in 1378 localized STS clinical samples, and searched for correlations with clinicopathological data, including disease-free survival (DFS), and with tumor immune features.ResultsCSPG4 expression was heterogeneous across samples. High expression was associated with younger patients' age, more frequent undifferentiated pleomorphic sarcoma and myxofibrosarcoma pathological subtypes, more frequent internal trunk tumor site, and more CINSARC high-risk samples. No correlation existed with pathological tumor size and grade, and tumor depth. Patients with high CSPG4 expression displayed 49% (95% CI 42-57) 5-year DFS versus 61% (95% CI 56-68) in patients with low expression (p = 3.17E-03), representing a 49% increased risk of event in the "CSPG4-high" group (HR = 1.49, 95% CI 1.14-1.94). This unfavorable prognostic value persisted in multivariate analysis, independently from other variables. There were significant differences in immune variables between "CSPG4-high" and "CSPG4-low" tumors. The "CSPG4-low" tumors displayed profiles suggesting higher anti-tumor cytotoxic immune response and higher potential vulnerability to immune checkpoint inhibitors (ICI). By contrast, the "CSPG4-high" tumors displayed profiles implying an immune-excluded tumor microenvironment, potentially induced by hypoxia, resulting from an immature chaotic microvasculature, and/or the presence of contractile myofibroblasts.ConclusionsPatients with "CSPG4-high" STS, theoretically candidate for CAR.CIKs, display shorter DFS and an immune environment unfavorable to vulnerability to CAR.CIKs, which could be improved by combining anti-angiogenic drugs able to normalize the tumor vasculature. By contrast, "CSPG4-low" STS are better candidates for immune therapy involving ICI.

Dataset Information

GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas.

Objective

Methods

Result

Conclusion

Publications

GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas.

Similar Datasets

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