1. Department of Health Statistics, School of Public Health, Fourth Military Medical University.
2. Department of Endoscopic Surgery, Xijing Hospital, Fourth Military Medical University.
3. Department of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University.
4. Department of General Surgery, Chinese PLA General Hospital.
5. Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University.
6. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University.
7. Department of Biochemistry and Molecular Biology, Fourth Military Medical University.
#Authors share co-first authorship.
*Authors share co-senior authorship.
Background: The current model for predicting prognosis and chemotherapy response of patients with gastric adenocarcinoma is the TNM staging system, which may lack adequate accuracy and evaluations of molecular features at the individual level. We aimed to develop a prediction model to assess the individualized prognosis and responsiveness to fluorouracil-based adjuvant chemotherapy.
Method: This retrospective study concluded 2 independent cohorts of patients with GAC. The expression of dysbindin was quantified and evaluated the association with the overall survival for GAC patients. A prediction model for postoperative overall survival was generated and internally and externally validated. The interaction between dysbindin expression and PACT was detected in advanced GAC patients.
Results: Of the 637 patients enrolled in the study, 425 were men (66.7%) with a mean (SD) age of 59.79 (9.81) years. High levels of dysbindin expression predicted a poor prognosis in patients with GAC. Multivariate analysis demonstrated dysbindin expression was an independent prognostic predictor of overall survival in the test, validation and combined cohorts. A prognostic predictive model incorporating age, dysbindin expression, pathological differentiation, Lauren's classification and the TNM staging system was established. This model had better predictive accuracy for overall survival than the traditional TNM staging system and was internally and externally validated. More importantly, advanced GAC patients with low dysbindin expression were likely to benefit from fluorouracil-based PACT.
Conclusion: The risk stratification model incorporating dysbindin expression and TNM staging system showed better predictive accuracy. Advanced GAC patients with low dysbindin expression revealed better response of fluorouracil-based adjuvant chemotherapy.
Keywords: dysbindin, overall survival, TNM stage, chemotherapy benefit