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

Lile He; Xiangyu Shi; Zhongyue Liu; Xiaolei Ren; Chenghao Zhang; Zhulin Yang; Zhihong Li

doi:10.2147/OTT.S222426

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

Onco Targets Ther. 2019 Oct 14:12:8411-8420. doi: 10.2147/OTT.S222426. eCollection 2019.

Authors

Lile He^{1

2}, Xiangyu Shi³, Zhongyue Liu¹, Xiaolei Ren¹, Chenghao Zhang¹, Zhulin Yang⁴, Zhihong Li^{1

2}

Affiliations

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

Abstract

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: DHFR; EAAT1; chondroma; chondrosarcoma; fetuin-A; immunohistochemistry.