10 年后高级软组织肉瘤中血栓调节蛋白 mRNA 的预后意义。

Prognostic Significance of Thrombomodulin mRNA in High-Grade Soft Tissue Sarcomas after 10 years.

机构信息

Department of Orthopedic Surgery, Mie University School of Medicine, Tsu City, Japan.

Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Japan.

出版信息

Orthop Surg. 2020 Dec;12(6):1726-1732. doi: 10.1111/os.12779. Epub 2020 Oct 4.

DOI:10.1111/os.12779

PMID:33015987

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7767767/

Abstract

OBJECTIVE

To elucidate the correlation between expression of thrombomodulin (TM) mRNA from 83 benign soft tissue tumors or soft tissue sarcomas (STS) and clinicopathological parameters and to analyze the outcome of high-grade STS patients after 10 years.

METHODS

Total RNA was extracted from 83 primary soft tissue tumors (15 benign tumors, 68 STS). TM mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase was measured with real-time quantitative polymerase chain reaction and compared to various clinicopathological parameters. The log-rank test and Cox proportional hazard analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival.

RESULTS

Thrombomodulin mRNA levels were not significantly different between benign tumors and STS. In STS, TM mRNA levels were not significantly different between histologically high-grade (n = 57) and low-grade (n = 11) tumors. Following analysis of high-grade STS at the 10-year follow-up, 21 patients had experienced a recurrence, 22 patients had experienced metastasis, and 23 patients had died of disease (DOD). TM levels were significantly higher in patients with metastasis or DOD patients. Receiver operating characteristic analysis for identifying 5-year and 10-year DOD determined the threshold for best sensitivity and specificity as 0.283. We divided patients into those with high (<0.283) and low (≤0.283) TM mRNA levels. Based on Kaplan-Meier analysis, a significant difference between the two groups was seen for recurrence-free survival (5 years: low = 76.6%, high = 53.1%, 10 years: low: 67.0%, high 39.8%, P = 0.0122) and metastasis-free survival (5 years: low = 86.3%, high = 40.2%, 10 years: low: 73.3%, high: 35.2%, P = 0.00023). Furthermore, the high TM group showed significantly worse prognosis than the low TM group (5 years: low = 90.1%, high = 42.3%, 10 years: low: 76.4%, high 31.3%, P = 0.00031). Thus, high levels of TM mRNA are associated with highly recurrent and metastatic potential and lead to poor prognosis. In multivariate Cox proportional hazard analysis, only high TM showed a significant difference in metastasis-free survival (hazard ratio: 4.33, 95% confidence interval 1.61-11.6, P = 0.00359) and overall survival (hazard ratio: 3.69, 95% confidence interval 1.49-10.5, P = 0.00569).

CONCLUSION

High levels of TM mRNA may be a significant predictor of recurrence, metastasis, and a poor outcome in STS patients after 10 years. TM is a candidate molecular marker and may be clinically useful for devising a therapeutic treatment strategy by prediction of prognosis.

摘要

目的

阐明 83 例良性软组织肿瘤或软组织肉瘤（STS）中血栓调节蛋白（TM）mRNA 的表达与临床病理参数之间的相关性，并分析 10 年后高级别 STS 患者的预后。

方法

从 83 例原发性软组织肿瘤（良性肿瘤 15 例，STS 68 例）中提取总 RNA。采用实时定量聚合酶链反应检测 TM mRNA，并用甘油醛-3-磷酸脱氢酶进行标准化，并与各种临床病理参数进行比较。采用对数秩检验和 Cox 比例风险分析评估无复发生存、无转移生存和总生存。

结果

良性肿瘤与 STS 之间 TM mRNA 水平无显著差异。在 STS 中，组织学高级别（n=57）和低级别（n=11）肿瘤之间 TM mRNA 水平无显著差异。对高级别 STS 进行 10 年随访分析后，21 例患者出现复发，22 例患者出现转移，23 例患者死于疾病（DOD）。TM 水平在发生转移或 DOD 的患者中明显升高。用于识别 5 年和 10 年 DOD 的受试者工作特征分析确定最佳灵敏度和特异性的阈值为 0.283。我们将患者分为 TM mRNA 水平高（<0.283）和低（≤0.283）两组。基于 Kaplan-Meier 分析，两组在无复发生存（5 年：低=76.6%，高=53.1%；10 年：低=67.0%，高=39.8%，P=0.0122）和无转移生存（5 年：低=86.3%，高=40.2%；10 年：低=73.3%，高=35.2%，P=0.00023）方面存在显著差异。此外，TM 高组的预后明显差于 TM 低组（5 年：低=90.1%，高=42.3%；10 年：低=76.4%，高=31.3%，P=0.00031）。因此，TM mRNA 水平高与高复发和转移潜能相关，并导致不良预后。在多变量 Cox 比例风险分析中，只有 TM 高显示出无转移生存（危险比：4.33，95%置信区间 1.61-11.6，P=0.00359）和总生存（危险比：3.69，95%置信区间 1.49-10.5，P=0.00569）方面的显著差异。