Correlation of Skp2 high expression with neoadjuvant chemotherapy resistance in patients with osteosarcoma
XU Duohui1 DING Lu2 YU Wei1 SONG Zhengnan1 BAI Jingping1
1.Department of Bone and Soft Tissue Oncology, the Third Clinical Medical College of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830000, China;
2.The first Department of Orthopedics, the Fifth Clinical Medical College of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830000, China
Abstract：Objective To explore the effect of Skp2 in neoadjuvant chemotherapy resistance of osteosarcoma. Methods Gene expression profiles of osteosarcoma and resistant osteosarcoma were collected from GSE126209, GSE16089 and TCGA datasets. The mechanisms of Skp2 resistance to osteosarcoma were identified. From February 2018 to June 2019, 17 patients with osteosarcoma admitted to the Third Clinical Medical College of Xinjiang Medical University were collected, non-drug resistance was defined as tumor cell necrosis rate (TCNR) ≥90%, and drug resistance was defined as TCNR < 90%, 11 cases of including non-drug resistant tumor tissues and 6 cases of drug resistant tumor tissues; 11 cases of non-drug-resistant paracancer tissues and 6 cases of drug-resistant paracancer tissues. RT-qPCR and Western-blot were used to detect mRNA and protein expression of Skp2 and related genes in osteosarcoma carcinoma tissues and adjacent tissues. Results The Skp2 was up-regulated in both osteosarcoma tissue and Methotrexate resistant cells. It was involved in cell cycle and FOXO pathway. Molecular experimental results showed that Skp2 and AKT expressions in drug-resistant osteosarcoma tissues were significantly increased (P ＜ 0.05); the expressions of p27, FOXO1 and E-Cadherin in resistant osteosarcoma were significantly lower (P ＜ 0.05). Cox analysis indicated that Skp2 (HR = 1.52, 95%CI: 0.67-3.46, P = 0.31), AKT (HR = 1.04, 95%CI: 0.48-2.28, P = 0.93), p21 (HR = 1.09, 95%CI: 0.51-2.34, P = 0.83), p27 (HR = 1.50, 95%CI: 0.67-3.38, P = 0.32) may be risk factors for prognosis of osteosarcoma. Conclusion Skp2 is involved in neoadjuvant chemotherapy resistance and in osteosarcomd and is associated with the cell cycle and FOXO pathway.
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2020, Vol. 17 
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