Abstract
Background: Gastric cancer ranks among the leading malignancies worldwide, noted for its high morbidity and mortality, and remains a significant challenge to global public health. Aim: To investigate the association between the expression of splicing factor 3b subunit 4 (SF3B4) and high mobility group box 1 (HMGB1) with the clinical characteristics and prognostic outcomes of gastric cancer patients. Methods: A retrospective cohort study was conducted involving 114 individuals diagnosed with gastric cancer and admitted to our institution from January 2020 to December 2021. A comparison group of 90 patients diagnosed with benign gastric disorders during the same period was also included. Expression levels of SF3B4 and HMGB1 were assessed using real-time quantitative polymerase chain reaction. Expression patterns were analyzed in relation to various clinicopathological features. Receiver operating characteristic curves were constructed to evaluate the ability of SF3B4 and HMGB1, alone and in combination, to predict unfavorable one-year outcomes. Multivariate logistic regression was utilized to identify independent predictors of mortality. Kaplan-Meier survival curves were generated to examine survival differences based on SF3B4 and HMGB1 expression levels. Results: Both SF3B4 and HMGB1 were markedly upregulated in tumor tissues of gastric cancer patients compared to adjacent normal tissues and to tissues from non-malignant gastric disease patients (a P < 0.05). Higher expression levels of these two genes were significantly associated with aggressive pathological features, including poor differentiation, tumor size > 5 cm, deep infiltration (T3-T4), lymph node involvement, and advanced clinical stage (III-IV) (a P < 0.05). Receiver operating characteristic analysis revealed that the combined use of SF3B4 and HMGB1 yielded an area under the curve of 0.914, surpassing the predictive performance of either marker alone (SF3B4: 0.776; HMGB1: 0.757). Multivariate analysis identified SF3B4 ≥ 1.45, HMGB1 ≥ 0.93, poor differentiation, larger tumor size, deeper invasion, lymph node metastasis, and advanced clinical tumor-node-metastasis staging as independent factors contributing to one-year mortality (a P < 0.05). Survival analysis indicated that patients with elevated SF3B4 and HMGB1 levels had a shorter median survival (25.74 ± 5.46 months) compared to those with lower expression levels (33.29 ± 6.71 months, log-rank = 10.534, a P < 0.05). Conclusion: Elevated SF3B4 and HMGB1 expression in gastric cancer tissue is significantly associated with tumor aggressiveness, worse prognosis, and reduced survival. These biomarkers may offer clinical value in stratifying patients by risk and in forecasting outcomes. Their combined assessment improves predictive accuracy for poor prognosis and may serve as a more effective tool than individual evaluation.