Background: Gastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.
Materials And Methods: We extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan-Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.
Results: Forty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33-2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.
Conclusion: A four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.
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http://dx.doi.org/10.3389/fonc.2021.584213 | DOI Listing |
Gastric Cancer
January 2025
Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Avenida Menendez Pelayo nro 4 accesorio, Valencia, Spain.
Introduction: Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries.
Material And Methods: Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries.
BMC Surg
January 2025
Department of General, Visceral and Transplantation Surgery, LMU University Hospital Munich, LMU Munich, Munich, Germany.
Background: Pancreatic ductal adenocarcinoma (PDAC) typically occurs in an older patient population. Yet, early-onset pancreatic cancer (EOPC) has one of the fastest growing incidence rates. This study investigated the influence of age and tumor location on postoperative morbidity and mortality in a large, real-world dataset.
View Article and Find Full Text PDFCurr Oncol Rep
January 2025
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa City, Chiba, Japan.
Purpose Of Review: Human epidermal growth factor receptor 2 (HER2) is a critical target in advanced gastric cancer (AGC). This review highlights the current treatment landscape, lessons learned from past clinical trials, and prospects for future treatment strategies for HER2-positive AGC.
Recent Findings: Trastuzumab had been the standard treatment for HER2-positive AGC for a decade, and subsequently, trastuzumab deruxtecan, an antibody-drug conjugate (ADC), emerged with an impressive response.
QJM
January 2025
Department of Dermatology, Dalian Dermatosis Hospital, Dalian, Liaoning, 116011, China.
Front Pharmacol
December 2024
Department of Vascular Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University/Second Military Medical University, Shanghai, China.
Background: Proton pump inhibitors (PPIs) are effective treatments for acid-related disorders but may pose tumor risks with long-term use. Current research on PPI-associated tumor adverse events (TAEs) is limited and inconclusive. This study aims to comprehensively analyze the relationship between PPIs and TAEs.
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