Identification of an Immune-Related BAT Signature for Predicting Adjuvant Chemotherapy Response and Overall Survival in Patients with Resected Ductal Adenocarcinoma of the Pancreas

• Published in: Journal of gastrointestinal surgery 2022-04, Vol.26 (4), p.869-886
• Main Authors: Pu, Ning, Chen, Qiangda, Yin, Hanlin, Zhang, Jicheng, Zhao, Guochao, Habib, Joseph R., Chen, Jie, Yu, Jun, Lou, Wenhui, Wu, Wenchuan
• Format: Article
• Language: English
• Subjects: Biomarkers; Biomarkers, Tumor - genetics; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - surgery; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Chemotherapy; Chemotherapy, Adjuvant; Gastroenterology; Gastrointestinal surgery; Gene expression; Genomes; Hospitals; Humans; Medical prognosis; Medicine; Medicine & Public Health; Original Article; Pancreas - pathology; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - surgery; Polymerase chain reaction; Prognosis; Proteins; Risk factors; Surgery
• ISSN: 1091-255X; 1873-4626
• DOI: 10.1007/s11605-021-05232-6

Background Adjuvant chemotherapy (ACT) is widely accepted in patients with pancreatic ductal adenocarcinoma (PDAC) after surgery; however, effective models for predicting ACT response are scarce. Thus, the objective of this study was to develop a novel signature for predicting its response and overall survival (OS) in resected PDAC patients. Methods A total of 50 PDAC patients with the transcriptome expression profiles, information about chemotherapy, and relevant clinical data were retrieved from the Cancer Genome Atlas (TCGA), and twenty-nine patients with tissue specimens and clinical data from our hospital were included as a validation. A novel gene signature was developed using bioinformatic differentially expressed genes (DEGs) analysis, Lasso-penalized Cox regression, and multivariate Cox regression studies. Results Between chemotherapy-resistant and chemotherapy-sensitive cohorts, 569 DEGs were identified, with 490 upregulated and 79 downregulated genes mainly specialized in the regulation of peptide/protein/hormone secretion, calcium ion homeostasis, and T cell activation regulation in biological processes. After Lasso-penalized Cox and multivariate Cox regression analysis, BAT (BCHE, ADH1A, and TNS4) signature was established to predict ACT response and OS. Moreover, BAT signature was verified as an independent risk factor for ACT response ( p  = 0.042) and OS (median OS: 17.5 months vs. 34.8 months, p  = 0.040) and significantly associated with immune infiltrations ( p