早期发作的结直肠癌与晚期发作的结直肠癌的分子特征:一个病例对照研究
Junwei Tang1, Wen Peng1, Chuanxing Tian1
1Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Colorectal Institute of Nanjing Medical University, Jiangsu Province Engineering Research Center of Colorectal Cancer Precision Medicine and Translational Medicine.
International journal of surgery (London, England)
|May 14, 2024
概括
早期结直肠癌 (EOCRC) 显示出更高的微卫星不稳定性-高 (MSI-H) 和明显的突变率. 这一发现有助于为EOCRC患者开发个性化的治疗方法.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 早发性结直肠癌 (EOCRC) 与晚发性结直肠癌 (LOCRC) 相比,预后较差,发病率增加.
- 了解EOCRC独特的分子特性对于确定特定的治疗点至关重要.
研究的目的:
- 通过将其与LOCRC进行比较来划分EOCRC独特的分子景观.
- 确定潜在的治疗点,并指导EOCRC的个性化治疗策略.
主要方法:
- 对11,344名结直肠癌患者 (578名EOCRC,10,766名LOCRC) 的分析,这些患者在2003年至2022年期间被诊断出结直肠癌.
- 对瘤突变和瘤突变负担 (TMB) 的下一代测序.
- 对于微卫星不稳定性 (MSI) 的PD-L1表达和毛细血管电泳的免疫组织化学.
主要成果:
- 在EOCRC病例中,MSI-H比率较高 (10.2%对LOCRC的2.2%),PD-L1表达率较高.
- EOCRC表现出明显的突变特征,包括MSI-H子组中的FBXW7,FAT1,ATM,ARID1A和KMT2B中的丰富突变.
- 与LOCRC相比,EOCRC患者,特别是MSI-H患者的TMB较高,差异化较差.
结论:
- EOCRC的特点是MSI-H的流行率显著高,并且具有独特的突变特征.
- 在EOCRC中增加的PD-L1表达与MSI状态相关.
- 这些分子区别为开发针对EOCRC管理的向治疗提供了潜力.
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