He Jun, Wang Mengyao, Wu Dandan, Fu Hao, Shen Xiaopei
Fujian Key Laboratory of Medical Bioinformatics, Department of Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China.
Key Laboratory Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou 350122, China.
Int J Mol Sci. 2024 Nov 27;25(23):12771. doi: 10.3390/ijms252312771.
FOLFIRI (5-FU, leucovorin, irinotecan) is the first-line chemotherapy for metastatic colorectal cancer (mCRC), but response rates are under 50%. This study aimed to develop a predictive signature for FOLFIRI response in mCRC patients. Firstly, Spearman's rank correlation and Wilcoxon rank-sum test were used to select chemotherapy response genes and gene pairs, respectively. Then, an optimization procedure was used to determine the final signature. A predictive signature consisting of three gene pairs (3-GPS) was identified. In the training set, 3-GPS achieved an accuracy of 0.94. In a validation set of 60 samples, predicted responders had significantly better progression-free survival than the predicted non-responders (HR = 0.47, = 0.01). A comparable result was observed in an additional validation set of 27 samples (HR = 0.06, = 0.02). The co-expressed genes of the signature were enriched in pathways associated with the immunotherapy response, and they interacted extensively with FOLFIRI-related genes. Notably, the expression of signature genes significantly correlated with various immune cell types, including plasma cells and memory-resting CD4+ T cells. In conclusion, the REO-based signature effectively identifies mCRC patients likely to benefit from FOLFIRI. Furthermore, these signature genes may play a crucial role in the chemotherapy.
FOLFIRI（5-氟尿嘧啶、亚叶酸钙、伊立替康）是转移性结直肠癌（mCRC）的一线化疗方案，但缓解率低于50%。本研究旨在开发一种预测mCRC患者对FOLFIRI反应的特征性标志物。首先，分别使用Spearman秩相关分析和Wilcoxon秩和检验来选择化疗反应基因和基因对。然后，采用优化程序确定最终的特征性标志物。确定了一个由三对基因组成的预测性特征性标志物（3-GPS）。在训练集中，3-GPS的准确率达到0.94。在一个包含60个样本的验证集中，预测的反应者的无进展生存期显著优于预测的无反应者（HR = 0.47，P = 0.01）。在另一个包含27个样本的验证集中也观察到了类似的结果（HR = 0.06，P = 0.02）。该特征性标志物的共表达基因在与免疫治疗反应相关的通路中富集，并且它们与FOLFIRI相关基因广泛相互作用。值得注意的是，特征性标志物基因的表达与多种免疫细胞类型显著相关，包括浆细胞和记忆静止CD4+ T细胞。总之，基于REO的特征性标志物能够有效识别可能从FOLFIRI治疗中获益的mCRC患者。此外，这些特征性标志物基因可能在化疗中发挥关键作用。
