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Roles Of EAAT1, DHFR, And Fetuin-A In The Pathogenesis, Progression And Prognosis Of Chondrosarcoma

Authors He L, Shi X, Liu Z, Ren X, Zhang C, Yang Z, Li Z

Received 9 July 2019

Accepted for publication 20 September 2019

Published 14 October 2019 Volume 2019:12 Pages 8411—8420

DOI https://doi.org/10.2147/OTT.S222426

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Shreya Arora

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Lile He,1,2 Xiangyu Shi,3 Zhongyue Liu,1 Xiaolei Ren,1 Chenghao Zhang,1 Zhulin Yang,4 Zhihong Li1,2

1Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Hunan Key Laboratory of Tumor Models and Individualized Medicine, Changsa, Hunan 410011, People’s Republic of China; 3Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 4Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China

Correspondence: Zhihong Li
Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Tel +86 139 7511 2458
Email lizhihong@csu.edu.cn

Aims: Chondrosarcoma (CS) is a high-morbidity, relatively common bone malignancy without well-established biomarkers. The proteins EAAT1, DHFR, and fetuin-A have been investigated in many cancers, but their specific relationship to CS has not been reported. The present study examined EAAT1, DHFR, and fetuin-A expression in CS and the clinicopathological significance of these proteins in CS pathogenesis, progression, and prognosis.
Methods: EAAT1, DHFR, and fetuin-A protein levels in 80 CS and 25 chondroma specimens were measured by immunohistochemistry and related to histological and clinical factors with chi-squared tests. Following univariate survival analysis, ROC curves calculation, and multivariate analysis.
Results: EAAT1, DHFR, and fetuin-A expression levels were significantly higher in the CS group than in the chondroma group (p < 0.05). Their immunopositivity rates were significantly greater in tissues with moderate or poor tumor differentiation, AJCC stage III or IV, Enneking stage II or III, and metastasis (p<0.05 or p<0.01 or p<0.001). Kaplan–Meier survival analysis showed significantly shorter survival in patients with moderately or poorly differentiated tumors, AJCC stage III or IV CS, Enneking stage II or III CS, metastasis, invasion, or EAAT1, DHFR, and fetuin-A immunopositivity (p < 0.05 or p < 0.001). Cox regression analysis showed that moderate or poor tumor differentiation, AJCC stage III or IV, Enneking stage II or III, metastasis, invasion, and EAAT1, DHFR, or fetuin-A immunopositivity correlated negatively with postoperative survival and positively with mortality (p < 0.05). The AUCs for EAAT1, DHFR, and fetuin-A were 0.654 (95% CI: 0.532–0.776, p = 0.025), 0.638 (95% CI: 0.519–0.756, p = 0.039), and 0.670 (95% CI: 0.556–0.784, p = 0.011), respectively.
Conclusion: EAAT1, DHFR, and fetuin-A may be important biomarkers of the pathogenesis and progression of CS and predictors of its prognosis.

Keywords: chondrosarcoma, chondroma, EAAT1, DHFR, fetuin-A, immunohistochemistry

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