软组织肉瘤患者的二代测序(NGS):诊疗价值、与中医药治疗的关系  

Next-generation sequencing(NGS)analysis in patients with soft tissue sarcomas:Diagnostic and therapeutic implications and their relationship with traditional Chinese medicine

作　　者：位子健 井源浩 李茹恬[2] WEI Zijian;JING Yuanhao;LI Rutian(The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital,Clinical College of Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Jiangsu Nanjing 210031,China;The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Jiangsu Nanjing 210008,China)

机构地区：[1]南京中医药大学中西医结合鼓楼临床医学院肿瘤中心,江苏南京210031 [2]南京大学医学院附属鼓楼医院肿瘤中心,江苏南京210008

出　　处：《现代肿瘤医学》2024年第20期3953-3958,共6页Journal of Modern Oncology

摘　　要：目的:探索二代测序(next-generation sequencing,NGS)技术在软组织肉瘤(soft tissue sarcoma,STS)患者中的诊疗价值,并结合NGS技术,探讨潜在的抗肉瘤中医治疗意义。方法:本研究采用NGS技术对30例不同亚型软组织肉瘤患者的肿瘤组织进行全面分析,共包含五个基因层面的检测:肿瘤体细胞变异:651个基因的全部外显子,65个基因的部分内含子;胚系变异:63个基因的全部外显子;肿瘤突变负荷(tumor mutation burden,TMB);微卫星不稳定性(microsatellite instability,MSI);PD-L1(22C3)蛋白表达。并结合临床实践进行数据解读。结果:肉瘤患者的基因突变主要分布在与细胞周期相关的基因和已知的致癌驱动基因中,其中有1例患者的手术病理诊断得到了NGS报告的修正。超过一半的患者具有可干预性突变,其中4例转移/复发性患者根据NGS报告进行了相应的靶向/免疫治疗,3例患者在临床治疗中获得了疾病控制,无进展生存时间(progression-free survival time,PFS)分别为6、6、12个月。结论:肉瘤组织基因测序可以进一步验证病理诊断;与肿瘤相关的遗传变异为现有的靶向治疗提供了科学依据并增加了新药靶点的发现潜力;报告中对免疫相关指标的检测为软组织肉瘤患者的免疫治疗选择和预后提供了依据;此外,我们还探讨了NGS报告中突变基因与中医治疗机制之间的关系;期望这些数据能够推动未来临床软组织肉瘤的精准/个体化医疗进展。Objective:To explore the diagnostic and therapeutic value of next-generation sequencing(NGS)technology in patients with soft tissue sarcoma(STS)and to investigate potential implications for anti-tumor traditional Chinese medicine(TCM)treatment.Methods:In this study,NGS technology was employed to comprehensively analyze tumor tissues from 30 patients with different subtypes of soft tissue sarcoma.The analysis encompassed five gene-level detections:Tumor cell mutations:all exons of 651 genes,and partial introns of 65 genes.Germline mutations:all exons of 63 genes.Tumor mutation burden(TMB).Microsatellite Instability(MSI).PD-L1(22C3)protein expression.Data interpretation was conducted in conjunction with clinical practice.Results:Gene mutations in sarcoma patients were predominantly distributed in genes related to the cell cycle and known oncogenic driver genes.One patient had their surgical pathology diagnosis revised based on the NGS report.Over half of the patients harbored actionable mutations,with four metastatic/recurrent patients undergoing targeted/immunotherapy based on NGS reports.Three patients achieved disease control during clinical treatment,with progression-free survival time of 6,6,and 12 months,respectively.Conclusion:The gene sequencing of sarcoma tissue can further validate pathological diagnosis.Genetic variations associated with tumors provide scientific basis for existing targeted therapies and increase the potential for discovering new drug targets.The detection of immune-related indicators in the report provides a basis for immunotherapy selection and prognosis for sarcoma patients.Furthermore,the relationship between mutated genes in NGS reports and the mechanisms of TCM treatment is explored.It is expected that these data will drive the advancement of precision/personalized medical treatment for clinical soft tissue sarcoma in the future.

关 键 词：软组织肉瘤 个性化医疗 二代测序 基因突变 中医药 

分 类 号：R738.6[医药卫生—肿瘤]