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Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years
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 pri...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons Australia, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767767/ https://www.ncbi.nlm.nih.gov/pubmed/33015987 http://dx.doi.org/10.1111/os.12779 |
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author | Asanuma, Kunihiro Nakamura, Tomoki Asanuma, Yumiko Okamoto, Takayuki Kakimoto, Takuya Yada, Yuki Hagi, Tomohito Kita, Kouji Nakamura, Koichi Matsumine, Akihiko Sudo, Akihiro |
author_facet | Asanuma, Kunihiro Nakamura, Tomoki Asanuma, Yumiko Okamoto, Takayuki Kakimoto, Takuya Yada, Yuki Hagi, Tomohito Kita, Kouji Nakamura, Koichi Matsumine, Akihiko Sudo, Akihiro |
author_sort | Asanuma, Kunihiro |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7767767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley & Sons Australia, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77677672020-12-28 Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years Asanuma, Kunihiro Nakamura, Tomoki Asanuma, Yumiko Okamoto, Takayuki Kakimoto, Takuya Yada, Yuki Hagi, Tomohito Kita, Kouji Nakamura, Koichi Matsumine, Akihiko Sudo, Akihiro Orthop Surg Clinical Articles 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. John Wiley & Sons Australia, Ltd 2020-10-04 /pmc/articles/PMC7767767/ /pubmed/33015987 http://dx.doi.org/10.1111/os.12779 Text en © 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Articles Asanuma, Kunihiro Nakamura, Tomoki Asanuma, Yumiko Okamoto, Takayuki Kakimoto, Takuya Yada, Yuki Hagi, Tomohito Kita, Kouji Nakamura, Koichi Matsumine, Akihiko Sudo, Akihiro Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years |
title | Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years |
title_full | Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years |
title_fullStr | Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years |
title_full_unstemmed | Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years |
title_short | Prognostic Significance of Thrombomodulin mRNA in High‐Grade Soft Tissue Sarcomas after 10 years |
title_sort | prognostic significance of thrombomodulin mrna in high‐grade soft tissue sarcomas after 10 years |
topic | Clinical Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767767/ https://www.ncbi.nlm.nih.gov/pubmed/33015987 http://dx.doi.org/10.1111/os.12779 |
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