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Identification of an Immune-Related BAT Signature for Predicting Adjuvant Chemotherapy Response and Overall Survival in Patients with Resected Ductal Adenocarcinoma of the Pancreas.
- Source :
-
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract [J Gastrointest Surg] 2022 Apr; Vol. 26 (4), pp. 869-886. Date of Electronic Publication: 2022 Jan 21. - Publication Year :
- 2022
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Abstract
- 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.<br />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.<br />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 < 0.05). Then, this signature was further validated as the independent risk factor for recurrence-free survival (RFS) in PDAC patients receiving postoperative ACT (median RFS: 9.0 months vs. not reached, p = 0.014), and tumor-infiltrating CD4 <superscript>+</superscript> and CD8 <superscript>+</superscript> T cells were further validated to be significantly decreased in tissues with higher BAT signature scores (p = 0.015 and 0.021, respectively).<br />Conclusion: The BAT signature is a novel formulated and independent risk factor for predicting ACT response and long-term survival in patients with resected PDAC. This signature could comprehensively reflect local immune-related response, tumor purity, potential biological behavior, and chemo drug susceptibility.<br /> (© 2021. The Society for Surgery of the Alimentary Tract.)
- Subjects :
- Biomarkers, Tumor genetics
CD8-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes pathology
Chemotherapy, Adjuvant
Humans
Pancreas pathology
Prognosis
Carcinoma, Pancreatic Ductal drug therapy
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal surgery
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms genetics
Pancreatic Neoplasms surgery
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4626
- Volume :
- 26
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
- Publication Type :
- Academic Journal
- Accession number :
- 35059985
- Full Text :
- https://doi.org/10.1007/s11605-021-05232-6