Background Soft-tissue sarcomas (STSs) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. We hypothesized that the Genomic Grade Index (GGI), a 108-gene signature previously developed in early-stage breast cancer, might improve the prognostic assessment of patients with early-stage STS. Patients and methods We collected gene expression and clinicopathological data of 678 operated STS, and searched for correlations between the GGI-based classification and clinicopathological variables, including the metastasis-free survival (MFS). Results Based on GGI, 275 samples (41%) were classified as 'GGI-low' and 403 (59%) as 'GGI-high'. The 'GGI-high' class was more associated with poor-prognosis features than the 'GGI-low' class: pathological grade 3 (P = 9.50E-11), undifferentiated sarcomas and leiomyosarcomas (P < 1.00E-06), location in extremities (P < 1.00E-06), and complex genetic profile (P = 2.1E-20). The 5-year MFS was 53% (95%CI 47-59) in the 'GGI-high' class versus 78% (95%CI 72-85) in the 'GGI-low' class (P = 3.02E-11), with a corresponding hazard ratio for metastatic relapse equal to 2.92 (95%CI 2.10-4.07; P = 2.23E-10). In multivariate analysis, the GGI-based classification remained significant, whereas the pathological grade did not. In fact, the GGI-based classification stratified the patients with pathological grades 1 and 2 and those with pathological grade 3 in two classes with different 5-year MFS. Comparison of the GGI and CINSARC multigene signatures revealed similar correlations with clinicopathological variables, which were, however, stronger with GGI than with CINSARC, a strong concordance (71%) in terms of low-risk or high-risk classifications, and independent prognostic value for MFS in multivariate analysis, suggesting complementary prognostic information. Conclusion GGI refines the prediction of MFS in operated STS and might improve the tailoring of adjuvant chemotherapy. Further clinical validation is warranted in larger retrospective, then prospective series, as well as the functional validation of relevant genes that could provide new therapeutic targets.

中文翻译：

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基因组等级指数可预测软组织肉瘤患者的术后临床结局。

背景技术软组织肉瘤（STS）是一组罕见，异质和侵袭性肿瘤，具有高转移风险和相对较少的有效全身疗法。我们假设先前在早期乳腺癌中发展的具有108个基因特征的基因组等级指数（GGI）可能会改善早期STS患者的预后评估。患者和方法我们收集了678例STS的基因表达和临床病理数据，并搜索了基于GGI的分类与临床病理变量之间的相关性，包括无转移生存期（MFS）。结果根据GGI，将275个样本（41％）分类为“ GGI低”，将403个样本（59％）分类为“ GGI高”。与“ GGI低”类相比，“ GGI高”类与预后较差的特征更多相关：病理等级3（P = 9.50E-11），未分化肉瘤和平滑肌肉瘤（P <1.00E-06），四肢位置（P <1.00E-06）和复杂的遗传特征（P = 2.1E-20）。``GGI高''类别的5年MFS为53％（95％CI 47-59），而``GGI低''类别则为78％（95％CI 72-85）（P = 3.02E-11 ），相应的转移复发风险比等于2.92（95％CI 2.10-4.07； P = 2.23E-10）。在多变量分析中，基于GGI的分类仍然很重要，而病理分级则没有。实际上，基于GGI的分类将病理等级为1和2以及病理等级为3的患者分为两个类别，分别具有不同的5年MFS。GGI和CINSARC多基因签名的比较显示与临床病理变量具有相似的相关性，即 但是，GGI比CINSARC更强，在低风险或高风险分类方面有很强的一致性（71％），并且在多变量分析中MFS具有独立的预后价值，提示补充的预后信息。结论GGI完善了手术STS中MFS的预测，并可能改善辅助化疗的适应性。需要进行更大范围的回顾性研究，然后再进行前瞻性研究，以及可能提供新治疗靶标的相关基因的功能验证，才能进一步进行临床验证。结论GGI完善了手术STS中MFS的预测，并可能改善辅助化疗的适应性。需要进行更大范围的回顾性研究，然后再进行前瞻性研究，以及可能提供新治疗靶标的相关基因的功能验证，才能进一步进行临床验证。结论GGI完善了手术STS中MFS的预测，并可能改善辅助化疗的适应性。需要进行更大范围的回顾性研究，然后再进行前瞻性研究，以及可能提供新治疗靶标的相关基因的功能验证，才能进一步进行临床验证。