Gastric cancer (GC) is one of the most prevalent and lethal malignancies globally, with over 1 million new cases reported annually [1,2]. It is characterized by invasiveness, heterogeneity, and poor prognosis [3]. Statistically, the 5-year survival rate of patients with stage IA and IB tumors who undergo surgical treatment ranges from 60 % to 80 % but declines to a disheartening 18–50 % among patients with stage III disease [4]. This imposes substantial economic burdens and impairs quality-of-life for affected patients [5]. Despite advances in diagnostic and treatment strategies, the survival rate of patients with GC has not significantly improved [6]. Therefore, identifying new therapeutic targets and reliable prognostic markers is imperative for tailoring personalized treatment plans, reducing patient burden, and improving clinical outcomes.

Stress granules (SGs) are key components of the cellular stress response [7]. These dynamic structures, composed of proteins and RNAs, form in response to various stressors and play crucial roles in gene expression regulation, translational control, and cell survival [8]. SGs are part of the cellular defense mechanisms against various stressors, including heat shock, hypoxia, oxidative stress, and viral infections [9]. Recent studies have highlighted the importance of SG-related regulators in cancer biology [10]. These regulators are involved in various cellular processes, such as mRNA stabilization, translation repression, and adaptive responses to environmental stressors [9]. Enhanced stress adaptation enables cancer cells to survive under harsh microenvironmental conditions [11]. ATXN2L, a novel SG regulator, promotes GC cell invasiveness and oxaliplatin resistance, making it a potential biomarker and therapeutic target [12]. Zhao et al. discovered that G3BP1, an SG assembly effector, may exert oncogenic effects by suppressing apoptosis and promoting chemoresistance in GC cells [13]. In GC, aberrant expression or dysfunction of SG-related factors can lead to tumor progression [14], highlighting their potential as therapeutic targets. However, comprehensive screening of SG-related genes influencing GC prognosis and exploration of their regulatory mechanisms remain lacking.

Therefore, this study aimed to identify SG-related prognostic markers using bioinformatic analyses and evaluate their performance in predicting outcomes in patients with GC. In addition, SG-related molecular subtypes were characterized to gain deeper insights into the interactions between SG-related genes and clinical prognosis, immune landscape, and drug sensitivity. Furthermore, in vitro experiments were conducted to validate the expression patterns and molecular functions of these prognostic genes. In summary, by focusing on SG-related regulatory factors, this study aimed to discover new biomarkers and therapeutic targets, ultimately contributing to a more effective and personalized management of GC.