Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Clin Colorectal Cancer. 2023 Dec;22(4):411-420.e1. doi: 10.1016/j.clcc.2023.07.004. Epub 2023 Jul 22.
Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression.
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.
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.
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.
新辅助放化疗（CRT）是治疗晚期直肠癌的标准治疗方法。然而，对于 CRT 的反应从完全缓解到零肿瘤消退不等。
在接受长程新辅助 CRT 治疗的 266 例晚期直肠癌患者的活检样本中，评估了肿瘤内芽殖（ITB）和肿瘤内 CD8+细胞密度对 CRT 反应和生存的影响。使用来自 174 例具有 RNA 测序数据的患者的数据，比较了 ITB 高和低的患者之间上皮-间质转化（EMT）标志物的表达。
62 例患者（23.3%）观察到高 ITB。ITB 与 CD8+细胞密度之间没有关联。多变量逻辑回归分析显示，高 CD8+细胞密度（OR，2.69；95%CI，1.45-4.98；P=0.002）与 CRT 反应良好相关，而高 ITB（OR，0.33；95%CI，0.14-0.80；P=0.014）与反应不良相关。生存的多变量 Cox 回归分析显示，高 CD8+细胞密度与更好的无复发生存（HR，0.41；95%CI，0.24-0.72；P=0.002）和总生存（HR，0.36；95%CI，0.17-0.74；P=0.005）相关，但 ITB 的显著性值为边缘性（无复发生存的 P=0.104，总生存的 P=0.163）。高和低 ITB 患者之间 EMT 相关基因的表达没有显著差异。
活检样本中的 ITB 和 CD8+细胞密度可作为预测接受新辅助 CRT 治疗的直肠癌患者治疗反应的有用生物标志物。
