Prognostic Significance of Thrombomodulin mRNA in High-Grade Soft Tissue Sarcomas after 10 years.
Prognostic Significance of Thrombomodulin mRNA in High-Grade Soft Tissue Sarcomas after 10 years.
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DOI：
10.1111/os.12779
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发表时间：
2020-12
影响因子：
2.1
通讯作者：
Sudo A
中科院分区：
文献类型：
--
作者：
Asanuma K;Nakamura T;Asanuma Y;Okamoto T;Kakimoto T;Yada Y;Hagi T;Kita K;Nakamura K;Matsumine A;Sudo A
目的：探讨83例良性软组织肿瘤或软组织肉瘤组织中血栓调节蛋白(TM)基因表达与临床病理参数的关系，分析高度恶性软组织肿瘤或软组织肉瘤患者10 年后的预后。提取83例原发软组织肿瘤(良性肿瘤15例，STS 68例)的总RNA。采用实时荧光定量聚合酶链式反应检测经3-磷酸甘油醛脱氢酶标化的TM基因的表达，并与临床病理参数进行比较。采用对数等级检验和COX比例风险分析评估无复发、无转移和总生存率。良性肿瘤与STS患者血栓调节蛋白基因表达水平差异无统计学意义。在STS中，组织学高级别(n= 57)和低级别(n= 11)肿瘤组织中TM基因表达水平无显著差异。根据10年随访的高级别STS分析，21例患者复发，22例患者发生转移，23例患者死于疾病(DOD)。在有转移或DOD的患者中，TM水平显著升高。用于识别5年和10年DOD的受试者操作特征分析确定最佳灵敏度和特异度的阈值为0.283。我们将患者分为高(0.283)和低(≤0.283)TM基因表达水平的患者。经Kaplan-Meier分析，两组无复发生存率(5 年：低=76.6%，高=53.1%，10 年：低：67.0%，高39.8%，P= 0.0122)和无转移生存率(5 年：低=86.3%，高=40.2%，10 年：低：73.3%，高：35.2%，P= 0.00023)有显著差异。高TM组的预后明显差于低TM组(5 年：低=90.1%，高=42.3%；10 年：低：76.4%，高31.3%，P= 0.00031)。因此，高水平的TM mRNA与高度复发和转移潜能相关，并导致不良预后。在多因素COX比例风险分析中，仅高TM组的无转移生存率(风险比：4.33，95%可信区间1.61~11.6，P= 0.00359)和总体生存率(风险比：3.6 9，95%可信区间1.49~10.5，P= 0.00569)差异有统计学意义。TMmRNA的高水平可能是STS患者10 年后复发、转移和不良预后的重要预测指标。TM是一种候选的分子标志物，可通过预测预后来指导临床治疗策略。
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. 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. 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). 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.
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影响因子：
6.2
作者：
Kraybill, William G.;Harris, Jonathan;Spiro, Ira J.;Ettinger, David S.;DeLaney, Thomas F.;Blum, Ronald H.;Lucas, David R.;Harmon, David C.;Letson, G. Douglas;Eisenberg, Burton
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作者：
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Ishii, H
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作者：
Tanaka, Kazuhiro;Mizusawa, Junki;Iwamoto, Yukihide
通讯作者：
Iwamoto, Yukihide
影响因子：
15.9
作者：
Zhang, YM;Weiler-Guettler, H;Nawroth, PP
通讯作者：
Nawroth, PP
影响因子：
5.6
作者：
CONWAY, EM;NOWAKOWSKI, B;STEINERMOSONYI, M
通讯作者：
STEINERMOSONYI, M