RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
治疗前活检中肿瘤出芽和 CD8 阳性 T 细胞密度作为晚期直肠癌新辅助放化疗反应的预测因子
英文原题：Intratumoral Budding and CD8-Positive T-cell Density in Pretreatment Biopsies as a Predictor of Response to Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer.
查看英文原题
Intratumoral Budding and CD8-Positive T-cell Density in Pretreatment Biopsies as a Predictor of Response to Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer.
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研究概要
活检样本中的 ITB 和 CD8+细胞密度可作为有用的生物标志物，用于预测接受新辅助 CRT 治疗的直肠癌患者的治疗反应。
中文摘要
背景
新辅助放化疗（CRT）是晚期直肠癌的标准治疗，但患者对CRT的应答不一，可从完全缓解到完全无肿瘤退缩。
材料与方法
研究评估了266例接受长程新辅助CRT的晚期直肠癌患者活检样本中，肿瘤内出芽（ITB）和肿瘤内CD8⁺细胞密度对治疗应答及生存的影响。研究利用174例患者的RNA测序数据，比较ITB高和低患者上皮-间质转化（EMT）标志物的表达。
结果
62例患者（23.3%）观察到高ITB。ITB与CD8⁺细胞密度无相关性。多变量逻辑回归分析显示，CD8⁺细胞密度较高与CRT应答较好相关（OR 2.69；95% CI 1.45–4.98；P=.002），而ITB较高与应答较差相关（OR .33；95% CI .14–.80；P=.014）。多变量Cox生存分析显示，CD8⁺细胞密度较高与更好的无复发生存期（HR .41；95% CI .24–.72；P=.002）和总生存期（HR .36；95% CI .17–.74；P=.005）相关；ITB的显著性则较弱（无复发生存期P=.104，总生存期P=.163）。ITB高低患者之间EMT相关基因表达无显著差异。
结论
直肠癌活检样本中的ITB和CD8⁺细胞密度可能成为预测接受新辅助CRT患者治疗应答的有用生物标志物。
展开英文摘要原文
BACKGROUND
Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression.
MATERIALS AND METHODS
The impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing.
RESULTS
High ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB.
CONCLUSION
ITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.
论文信息
- 作者
- Sano S、Akiyoshi T、Yamamoto N、Hiyoshi Y、Mukai T、Yamaguchi T、Nagasaki T、Taketomi A
- 第一作者单位
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.Japan
- 通讯作者单位
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: takashi.akiyoshi@jfcr.or.jp.Japan
- 文献类型
- 非美国政府资助研究
- 期刊
- Clinical colorectal cancer2023 Dec
- 原文标识
- PubMed 37516615 · DOI 10.1016/j.clcc.2023.07.004