J Cancer 2020; 11(12):3623-3633. doi:10.7150/jca.37393

Research Paper

Identification of tumorigenicity-associated genes in osteosarcoma cell lines based on bioinformatic analysis and experimental validation

Shaojie Jiang1,2*, Fei Zhou1*, Yanhua Zhang3, Weiping Zhou4, Linghua Zhu5, Miaofeng Zhang6, Jingfeng Luo1, Rui Ma7, Xiufang Xu2, Jiying Zhu2, Xue Dong1, Shuangling Zhang1, Jie Fang8, Jihong Sun1✉, Xiaoming Yang1,9✉

1. Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
2. School of Medical Imaging, Hangzhou Medical College, Hangzhou, Zhejiang, 310013, China.
3. Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
4. Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
5. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
6. Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
7. Department of Surgery, Zhejiang University Hospital, Zhejiang University, Hangzhou, Zhejiang 310027, China
8. Key Laboratory of Experimental Animal and Safety Research, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, China.
9. Image-Guided Bio-Molecular Intervention Research, Department of Radiology, University of Washington School of Medicine, Seattle, Washington, 98109, USA.
*Shaojie Jiang and Fei Zhou contributed equally to this work.

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Citation:
Jiang S, Zhou F, Zhang Y, Zhou W, Zhu L, Zhang M, Luo J, Ma R, Xu X, Zhu J, Dong X, Zhang S, Fang J, Sun J, Yang X. Identification of tumorigenicity-associated genes in osteosarcoma cell lines based on bioinformatic analysis and experimental validation. J Cancer 2020; 11(12):3623-3633. doi:10.7150/jca.37393. Available from http://www.jcancer.org/v11p3623.htm

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Abstract

Osteosarcoma is the most common primary malignant tumor of bone. Tumorigenic investigation of osteosarcoma cell lines may facilitate preclinical studies of targeted therapy. Therefore, the aim of this study was to explore the tumorigenicity-associated genes in osteosarcoma cells. We found that 138 genes were highly expressed and 86 genes were lowly expressed in highly tumorigenic osteosarcoma cell lines (143B, MNNG/HOS, and SJSA-1) compared with poorly tumorigenic osteosarcoma cell lines (MG-63, Saos-2, and U-2 OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that highly expressed genes were associated with amino acids and energy metabolism, while lowly expressed genes were associated with cell cycle and DNA replication. Gene Ontology (GO) analysis showed that highly expressed genes were associated with endoplasmic reticulum stress response and aggrephagy, whereas lowly expressed genes were correlated with extracellular matrix assembly and DNA damage response. Further analysis identified six highly expressed genes and six lowly expressed genes. Three of highly expressed genes (DDX10, FOXA2, and HEY1) were correlated with poor prognosis, while three of lowly expressed genes (CYP26B1, GP1BB, and IFI44) showed the opposite trend in patients with osteosarcoma. Knockdown of HEY1 significantly inhibited the tumorigenicity of 143B cells in BALB/c nude mice.

Keywords: osteosarcoma, bioinformatic analysis, tumorigenicity, HEY1, prognosis