TRIM68, PIKFYVE, and DYNLL2: The Possible Novel Autophagy- and Immunity-Associated Gene Biomarkers for Osteosarcoma Prognosis

• Main Authors: Jie Jiang, Dachang Liu, Guoyong Xu, Tuo Liang, Chaojie Yu, Shian Liao, Liyi Chen, Shengsheng Huang, Xuhua Sun, Ming Yi, Zide Zhang, Zhaojun Lu, Zequn Wang, Jiarui Chen, Tianyou Chen, Hao Li, Yuanlin Yao, Wuhua Chen, Hao Guo, Chong Liu, Xinli Zhan
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-04-01
• Series: Frontiers in Oncology
• Subjects: osteosarcoma; autophagy; immune infiltration; prognostic biomarkers; quantitative reverse transcription PCR; Immunohistochemistry
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2021.643104/full

IntroductionOsteosarcoma is among the most common orthopedic neoplasms, and currently, there are no adequate biomarkers to predict its prognosis. Therefore, the present study was aimed to identify the prognostic biomarkers for autophagy-and immune-related osteosarcoma using bioinformatics tools for guiding the clinical diagnosis and treatment of this disease.Materials and MethodsThe gene expression and clinical information data were downloaded from the Public database. The genes associated with autophagy were extracted, followed by the development of a logistic regression model for predicting the prognosis of osteosarcoma using univariate and multivariate COX regression analysis and LASSO regression analysis. The accuracy of the constructed model was verified through the ROC curves, calibration plots, and Nomogram plots. Next, immune cell typing was performed using CIBERSORT to analyze the expression of the immune cells in each sample. For the results obtained from the analysis, we used qRT-PCR validation in two strains of human osteosarcoma cells.ResultsThe screening process identified a total of three genes that fulfilled all the screening criteria. The survival curves of the constructed prognostic model revealed that patients with the high risk presented significantly lower survival than the patients with low risk. Finally, the immune cell component analysis revealed that all three genes were significantly associated with the immune cells. The expressions of TRIM68, PIKFYVE, and DYNLL2 were higher in the osteosarcoma cells compared to the control cells. Finally, we used human pathological tissue sections to validate the expression of the genes modeled in osteosarcoma and paracancerous tissue.ConclusionThe TRIM68, PIKFYVE, and DYNLL2 genes can be used as biomarkers for predicting the prognosis of osteosarcoma.