The role of GP73 in predicting overall survival and chemotherapy response in locally advanced gastric cancer: a retrospective cohort study

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-related mortality globally, with a 5-year survival rate remaining below 50% despite advancements in treatment. The standard care for locally advanced GC includes curative gastrectomy combined with perioperative chemotherapy. Different factors may influence chemotherapy responses, underscoring the need for biomarkers to tailor treatment. GP73, a Golgi-associated protein, has been implicated in cancer progression and prognosis, though its role in GC remains poorly understood. This study aimed to evaluate the association between pretreatment GP73 expression and overall survival (OS) and chemotherapy response in locally advanced GC patients. METHODS: This was a retrospective study of 92 locally advanced GC patients who received neoadjuvant chemotherapy and underwent surgery between 2017 and 2024. GP73 expression was assessed in pretreatment biopsy samples via immunohistochemistry. Clinicopathological data were analyzed, and the correlation between GP73 expression and survival, as well as chemotherapy response, was evaluated. Tumor regression was graded using the Mandard Tumor Regression Grade scale. Continuous variables were demonstrated as median and interquartile range. RESULTS: High GP73 expression was observed in 64% of patients and correlated with poor tumor differentiation and reduced likelihood of radical surgery. Univariate analysis revealed that high GP73 expression was significantly associated with poorer overall survival (p < 0.001). Multivariate Cox model identified high GP73 status as an independent prognostic factor for poor OS (HR 4.53, p < 0.001). However, no significant correlation was found between GP73 expression and chemotherapy response (p = 0.32). CONCLUSIONS: This study suggests that high pretreatment GP73 expression is a marker of poor prognosis in locally advanced GC, linked to poorer survival and less favorable tumor characteristics. These results highlight the need for personalized treatment strategies incorporating GP73 and other clinicopathological factors to optimize outcomes for GC patients.