■食管鳞状细胞癌(ESCC)新辅助治疗的选择存在争议。本研究旨在通过建立新辅助免疫化疗(NICT)疗效预测模型,为临床治疗方案选择提供依据。
■对30例患者进行了回顾性分析,根据是否达到主要病理缓解(MPR)分为有反应和无反应组。通过下一代测序(NGS)和多重免疫荧光(mIF)分析两组之间基因和免疫微环境的差异。通过LASSO回归和ROC曲线选择与疗效最密切相关的变量建立预测模型。前瞻性收集另外48名患者作为验证集,以验证模型的有效性。
■NGS提出了七个差异基因(ATM,ATR,BIVM-ERCC5,MAP3K1,PRG,RBM10、TSHR)两组间比较(P<0.05)。mIF表明CD3+的数量和位置存在显著差异,PD-L1+,CD3+PD-L1+,CD4+PD-1+,CD4+LAG-3+,CD8+LAG-3+,两组治疗前LAG-3+比较(P<0.05)。动态mIF分析还表明,CD3+,CD8+,两组治疗后CD20+均升高,反应组CD8+和CD20+增加更为显著(P<0.05),PD-L1+下降更显著(P<0.05)。通过LASSO回归和ROC曲线选择与疗效最密切相关的三个变量:肿瘤面积PD-L1+(AUC=0.881),CD3+PD-L1+(AUC=0.833),和CD3+(AUC=0.826),并建立了预测模型。模型在训练集(AUC=0.938)和验证集(AUC=0.832)中均显示出高性能。与传统的CPS评分标准相比,该模型的准确性显着提高(83.3%对70.8%),灵敏度(0.625对0.312),和特异性(0.937vs0.906)。
■NICT治疗可能通过富集免疫细胞和激活耗尽的T细胞来发挥抗肿瘤作用。肿瘤面积CD3+,PD-L1+,CD3+PD-L1+与疗效密切相关。包含这三个变量的模型可以准确预测治疗结果,为新辅助治疗方案的选择提供可靠依据。
UNASSIGNED: The choice of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) is controversial. This study aims to provide a basis for clinical treatment selection by establishing a predictive model for the efficacy of neoadjuvant immunochemotherapy (NICT).
UNASSIGNED: A retrospective analysis of 30 patients was conducted, divided into Response and Non-response groups based on whether they achieved major pathological remission (MPR). Differences in genes and immune microenvironment between the two groups were analyzed through next-generation sequencing (NGS) and multiplex immunofluorescence (mIF). Variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves to establish a predictive model. An additional 48 patients were prospectively collected as a validation set to verify the model\'s effectiveness.
UNASSIGNED: NGS suggested seven differential genes (ATM, ATR, BIVM-ERCC5, MAP3K1, PRG, RBM10, and TSHR) between the two groups (P < 0.05). mIF indicated significant differences in the quantity and location of CD3+, PD-L1+, CD3+PD-L1+, CD4+PD-1+, CD4+LAG-3+, CD8+LAG-3+, LAG-3+ between the two groups before treatment (P < 0.05). Dynamic mIF analysis also indicated that CD3+, CD8+, and CD20+ all increased after treatment in both groups, with a more significant increase in CD8+ and CD20+ in the Response group (P < 0.05), and a more significant decrease in PD-L1+ (P < 0.05). The three variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves: Tumor area PD-L1+ (AUC= 0.881), CD3+PD-L1+ (AUC= 0.833), and CD3+ (AUC= 0.826), and a predictive model was established. The model showed high performance in both the training set (AUC= 0.938) and the validation set (AUC= 0.832). Compared to the traditional CPS scoring criteria, the model showed significant improvements in accuracy (83.3% vs 70.8%), sensitivity (0.625 vs 0.312), and specificity (0.937 vs 0.906).
UNASSIGNED: NICT treatment may exert anti-tumor effects by enriching immune cells and activating exhausted T cells. Tumor area CD3+, PD-L1+, and CD3+PD-L1+ are closely related to therapeutic efficacy. The model containing these three variables can accurately predict treatment outcomes, providing a reliable basis for the selection of neoadjuvant treatment plans.