微环境变化表明,在早期发病的结直肠癌患者中,潜在的亚临床肠组织损伤可能存在
Sean G Kraus1,2, Katherine A Johnson1,2, Philip B Emmerich1,2
1Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
早期发病的结直肠癌 (CRC) 与晚期发病的CRC具有相似的遗传和瘤微环境特征. 然而,在相邻的正常组织中增加的versican (VCAN) 和α-光滑肌肉动蛋白 (αSMA) 可能表明炎症是EAO CRC的潜在原因.
科学领域:
- 在瘤学瘤学.
- 癌症基因组学 癌症基因组学
- 免疫学 免疫学 免疫学
背景情况:
- 结肠直肠癌 (CRC) 发病率在整体上下降,这是由于查的改善.
- 然而,早期发病的CRC (EAO CRC;年龄<50岁) 发病率正在上升.
- 了解EAO和晚年发病的CRC (LAO CRC) 之间的生物学差异对于确定病因因素至关重要.
研究的目的:
- 为了描述EAO CRC与LAO CRC的遗传变化.
- 分析EAO和LAOCRC之间的瘤微环境 (TME) 差异.
- 识别有助于EAOCRC发展的潜在生物因素.
主要方法:
- 针对性DNA测序用于评估60名EAO CRC和93名LAO CRC患者的突变.
- 免疫组织化学和免疫光学被用来评估TME差异.
- 在癌症基因组图谱 (TCGA) 大肠直肠腺癌队列 (82名EAOvs510名LAO患者) 中分析了转录变化.
主要成果:
- 在EAOCRC中,KRAS和BRAF突变的发生较少.
- 基因组丰富分析揭示了EAO CRCs中下调的免疫相关途径.
- 虽然CD8+瘤透淋巴细胞 (TILs) 类似,但LAO患者有更多的CD4+TIL和Th1-极化CD4. EAO患者在相邻的正常组织中表现出更大的Versican (VCAN) 积累趋势和降低的α-平滑肌动蛋白 (αSMA) 的趋势.
结论:
- 已建立的EAO和LAOCRC具有相似的突变配置文件和关键的TME特征.
- 邻近正常结肠中的高VCAN和αSMA表达表明与增加的亚临床肠道炎症相关的因素.
- 需要进一步的机制研究来优先考虑这些发现作为EAO瘤发生的潜在病因因素.
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