一种类似于DNA损伤反应的表型在发病时定义了三分之一的结肠癌
Stefania Mauro1, Maddalena M Bolognesi2, Nicoletta Villa3
1Pathology, Vimercate Hospital, ASST-Brianza, Vimercate, Italy.
概括
结肠腺癌 (COAD) 的一个亚组表现出协调的DNA损伤反应 (DDR),独立于已知的标记物. 这种DDR + COAD子组可能通过利用DNA修复途径提供新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 结肠腺癌 (COAD) 的治疗选择有限,特别是在非超变的病例中.
- 在COAD中确定个性化干预的新治疗目标和策略至关重要.
研究的目的:
- 调查DNA损伤反应 (DDR) 在未经治疗的COAD患者队列中的存在和特征.
- 在COAD中探索DDR与其他生物因素和临床参数的关联.
主要方法:
- 多重免疫光和免疫组织化学被用来检测DDR复杂蛋白质 (γH2AX,pCHK2,PNBS1).
- 分析包括I型干扰素反应,T淋巴细胞透 (TILs),不匹配修复缺陷 (MMRd) 和染色体20q复制数变异通过FISH.
- 分析了246例未经治疗的COAD病例,并进行了临床随访.
主要成果:
- 33.7%的COAD病例在静止腺体中表现出协调的DDR,无论TP53状态,20q异常或I型IFN反应.
- 临床病理学参数,TIL和对基于5FU的化疗的反应在DDR+和DDR-病例之间没有差异.
- 具有不匹配修复缺陷 (MMRd) 的DDR+病例优先保留野生型MLH1.1.
结论:
- 结肠腺癌表现出一个独特的DDR+亚组,与当前的诊断,预后或治疗类别不一致.
- 这个DDR+COAD子组通过利用DNA损伤修复途径,为新的向治疗机会提供了潜在的潜力.
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