Purpose: Neoadjuvant immunochemotherapy (NAIC) markedly induces pathologic regression in locally advanced gastric adenocarcinoma. However, specific biomarkers are still lacking to effectively identify the beneficiary patients for NAIC.
Patients And Methods: A prospective, single-arm, phase II study was conducted to treat locally advanced gastric adenocarcinoma with NAIC (NCT05515796). Correlation between clinicopathologic characteristics and neoadjuvant efficacy was investigated. Bulk RNA sequencing data from 104 samples (from 75 patients in two independent cohorts) and single-cell RNA sequencing data from 105 treatment-naïve gastric adenocarcinomas were comprehensively analyzed to decipher the association of epithelial and microenvironmental characteristics and clinical responses.
Results: The prespecified primary endpoints were achieved: pathologic complete regression rate was 30%, major pathologic regression rate was 43%, and the regimen was well tolerated. Analysis of baseline clinical-pathologic parameters revealed the intestinal subtype of Lauren's classification as a key feature stratifying patients with increased sensitivity to NAIC. Mechanistically, an increased pool of DNA damage repair-active cancer cells and enrichment of CLEC9A+ dendritic cells in the tumor microenvironment were associated with enhanced responsiveness of the intestinal subtype gastric adenocarcinoma to NAIC. More importantly, an intestinal subtype-specific signature model was constructed by the machine learning algorithm NaiveBayes via integrating the transcriptomic features of both DNA damage repair-active cancer cells and CLEC9A+ dendritic cells, which accurately predicted the efficacy of NAIC in multiple independent gastric adenocarcinoma cohorts.
Conclusions: Intestinal subtype is a histologic biomarker of enhanced sensitivity of gastric adenocarcinoma to NAIC. The intestinal subtype-specific signature model is applicable to guide NAIC for patients with locally advanced gastric adenocarcinoma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/1078-0432.CCR-24-2436 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unraveling the Role of Ubiquitin-Conjugating Enzyme UBE2T in Tumorigenesis: A Comprehensive Review.
Cells
December 2024
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China.
Ubiquitin-conjugating enzyme E2 T (UBE2T) is a crucial E2 enzyme in the ubiquitin-proteasome system (UPS), playing a significant role in the ubiquitination of proteins and influencing a wide range of cellular processes, including proliferation, differentiation, apoptosis, invasion, and metabolism. Its overexpression has been implicated in various malignancies, such as lung adenocarcinoma, gastric cancer, pancreatic cancer, liver cancer, and ovarian cancer, where it correlates strongly with disease progression. UBE2T facilitates tumorigenesis and malignant behaviors by mediating essential functions such as DNA repair, apoptosis, cell cycle regulation, and the activation of oncogenic signaling pathways.
View Article and Find Full Text PDFComplications Following Open Versus Minimally Invasive Resection of Gastric Adenocarcinoma.
J Surg Oncol
January 2025
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Background And Objectives: Gastric adenocarcinoma (GA) is commonly treated with open or minimally invasive surgery (MIS). The preferred surgical approach remains unclear. This study sought to assess utilization over time, compare complication rates by surgical approach, and identify predictors of experiencing complications.
View Article and Find Full Text PDFArtificial Intelligence-Guided Identification of IGFBP7 as a Critical Indicator in Lactic Metabolism Determines Immunotherapy Response in Stomach Adenocarcinoma.
J Cell Mol Med
January 2025
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Due to considerable tumour heterogeneity, stomach adenocarcinoma (STAD) has a poor prognosis and varies in response to treatment, making it one of the main causes of cancer-related mortality globally. Recent data point to a significant role for metabolic reprogramming, namely dysregulated lactic acid metabolism, in the evolution of STAD and treatment resistance. This study used a series of artificial intelligence-related approaches to identify IGFBP7, a Schlafen family member, as a critical factor in determining the response to immunotherapy and lactic acid metabolism in STAD patients.
View Article and Find Full Text PDFMetastatic pancreatic cancer now in remission: a case report and literature review.
Discov Oncol
January 2025
Hematology Oncology Associates of CNY, Syracuse, USA.
Pancreatic cancer is a highly aggressive malignancy with the majority of patients presenting at a late stage with unresectable or metastatic disease. Even with first line treatment, median survival is approximately 11 months in patients with advanced PDAC. This report details the unique case of a patient that presented with peritoneal metastases from an adenocarcinoma of the body of the pancreas, had a remarkable response to palliative chemotherapy and is alive without evidence of disease 12 months following cessation of all active treatment.
View Article and Find Full Text PDFHost tissue factors predict immune surveillance and therapeutic outcomes in gastric cancer.
Cancer Immunol Res
January 2025
Memorial Sloan Kettering Cancer Center, New York, NY, United States.
The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma-an aggressive cancer often linked to chronic inflammation-remains poorly understood. We leveraged high-dimensional spectral cytometry to generate a comprehensive single-cell immune landscape of tumors, normal tissue, and lymph nodes from patients in the Western Hemisphere with gastric adenocarcinoma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!