骨肉瘤预后相关致病基因的研究进展

Research progress on prognosis-related pathogenic genes of osteosarcoma

骨肉瘤是一种罕见的肿瘤,任何年龄均可诊断,全球范围内其发病年龄呈双峰分布,第一个高峰出现在15~19岁(8例/百万/年),第二个高峰出现在75~79岁(6例/百万/年)[1-2]。常发生在股骨(42%)、胫骨(19%)和肱骨(10%),化疗出现之前,约74%[3]的局部骨肉瘤患者在1年内出现肺转移。在20世纪70年代,引入联合化疗,即基于甲氨蝶呤、顺铂、阿霉素(可添加异环磷酰胺)的一线化疗[4-5]及其它药物如干扰素[4]的强化治疗后,局部骨肉瘤患者的5年生存率提高至60%。目前,对于患可切除骨肉瘤的患者,最常见治疗方法包括术前新辅助化疗及术后辅助化疗。对于化疗不敏感、转移及复发的患者其5年生存率低于20%[4]。

Osteosarcoma is a highly aggressive malignant tumor and its treatment remains a great challenge due to its high heterogeneity nature and complex pathogenesis.Over the past 20 years,there has been no improvement in prognosis with first-line chemotherapeutic agents and clinical outcomes.There is no effective anticancer drug for patients with drug-resistant,metastatic,and recurrent osteosarcoma,so new approaches are needed to improve prognosis.With the development of biotechnology and bioinformatics in recent years,research on osteosarcoma has made progress.Among them,the pathogenic genes and signaling pathways of osteosarcoma are the focus and hotspot of research.Understanding cancer biology helps to develop more effective detection and treatment methods,while the identification of pathogenic genes,especially driver genes,is one of the keys.The development of sequencing technology has promoted the identification of somatic mutations and copy number changes in osteosarcoma.Due to its high heterogeneity and low incidence,the research on the nature and quantity of driver genes related to the mechanism of osteosarcoma onset,invasion,metastasis,and prognosis is still in its early stages.This article reviews the pathogenic genes of osteosarcoma,biological functions,regulatory mechanisms,mutation characteristics,as well as the relevant signaling pathways and targeted therapies,hoping to provide hints of genes that classify patients into different therapeutic options.Among them,driver genes such as TP53,RB1,CDKN2A are considered to play an important role in the development of osteosarcoma,while genes such as ATRX,MDM2,PTEN,BRCA1/2,Rab22a have also been proven to be closely related to osteosarcoma development.