Predicting the efficacy of neoadjuvant chemoradiotherapy combined with immunotherapy for rectal cancer using untargeted metabolomics
10.3760/cma.j.cn115396-20241017-00317
- VernacularTitle:基于非靶向代谢组学预测新辅助放化疗联合免疫治疗直肠癌疗效研究
- Author:
Jingxin MA
1
;
Shengbo SUN
;
Yan GAO
;
Jianrong SU
;
Hongwei YAO
Author Information
1. 首都医科大学附属北京友谊医院临床检验中心，北京 100050
- Keywords:
Metabolomics;
Chemoradiotherapy;
Immunotherapy;
Rectal neoplasms;
Forecasting
- From:
International Journal of Surgery
2025;52(1):33-39
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the potential value of gut microbiota metabolites in predicting the efficacy of neoadjuvant chemoradiotherapy combined with immunotherapy in patients with locally advanced rectal cancer.Methods:Prospectively collected case data from 32 patients with locally advanced rectal patients, who underwent total mesorectal excision at Beijing Friendship Hospital, Capital Medical University, between October 2021 and August 2022. Among these patients, 18 (56.25%) were male and 14 (43.75%) were female, with ages ranging from 37 to 79 years and a mean age of (61.69±8.73) years. Postoperative pathological response was evaluated using the Tumor Regression Grade (TRG), dividing the patients into two groups: an efficacious group (ypT 0N 0, n=14) and a non-efficacious group (non-ypT 0N 0, n=18). Stools from 14 patients in the efficacious group and 18 patients in the non-efficacious group, who had experienced neoadjuvant chemoradiotherapy combined with immunotherapy, were collected before treatment. Metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry, and pathway enrichment analysis was performed. A random forest model was constructed based on the differential metabolites. The data were analyzed by using R4.1.1 and 26.0 software. Results:Through untargeted metabolomics analysis, 2′-Deoxyinosine and albiflorin were enriched in the responders, while Sorbitan monooleate, 2-(Formylamino) Benzoic Acid, and 12-Hydroxydodecanoic acid were enriched in the non-responders ( P<0.05); Arachidonic acid metabolism and tryptophan metabolism were enriched, and the AUC for the model was 0.976. Conclusions:Rectal cancer patients with or without complete postoperative pathological remission exhibit differences in the metabolites of their intestinal microbiome prior to undergoing neoadjuvant chemoradiotherapy combined with immunotherapy. The identified differential metabolites have the potential to serve as predictive biomarkers for treatment efficacy.
