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

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.

• Authors: Kunihiro Asanuma, Tomoki Nakamura, Yumiko Asanuma, Takayuki Okamoto, Takuya Kakimoto, Yuki Yada, Tomohito Hagi, Kouji Kita, Koichi Nakamura, Akihiko Matsumine, Akihiro Sudo
• Journal: Orthopaedic surgery (Orthop Surg) Vol. 12 Issue 6 Pg. 1726-1732 (Dec 2020) ISSN: 1757-7861 [Electronic] Australia
• PMID: 33015987 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Chemical References

• RNA, Messenger
• Thrombomodulin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Predictive Value of Tests
• Prognosis
• RNA, Messenger (metabolism)
• ROC Curve
• Sarcoma (genetics)
• Soft Tissue Neoplasms (genetics)
• Thrombomodulin (genetics)
• Young Adult