Expression level of Stanniocalcin 2 in gastric cancer patients and its predictive value for resistance to immunotherapy

Lin Huiling; Meng Jiarong; Yu Le; Zhu Qigan

doi:10.3760/j.issn.1673-4777.2026.04.007

Abstract：Objective To investigate the expression level of Stanniocalcin 2(STC2)in gastric cancer patients and its predictive value for resistance to immunotherapy.Methods A total of 148 gastric cancer patients admitted to the 909th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from April 2022 to April 2024 were enrolled as research subjects.Reverse transcription real-time fluorescent quantitative polymerase chain reaction was used to detect the relative expression of STC2 mRNA in gastric cancer tissues and paired paracancerous tissues(non-tumor gastric mucosal tissues ≥ 5 cm from the tumor edge).Immunohistochem-istry was performed to detect STC2 protein expression,and patients were divided into the high STC2 expression group(90 cases)and low STC2 expression group(58 cases)according to staining intensity and the proportion of positive cells.The clinicopathological data of patients were collected,and the occurrence of immunotherapy resist-ance was observed.Receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of STC2 expression level for immunotherapy resistance.Correlation heatmap was used to analyze the association between STC2 expression and tumor immune microenvironment indicators,including the infiltration ratios of CD8+T cells,CD4+T cells and B cells,the positive rate of programmed cell death protein 1(PD-1)in T cells,the infiltration ratios of regulatory T cells(Treg,marked by FOXP3+)and macrophages(marked by C D68),as well as the positive rate of programmed cell death ligand 1(PD-L1)on the surface of tumor cells.Results The relative expression of STC2 mRNA in gastric cancer tissues was(2.7±0.7),which was significantly higher than that in paracancerous tissues(1.0±0.3),with a statistically significant difference(t=27.035,P＜0.001).The positive expression rate of STC2 in gastric cancer tissues(58.1％)was higher than that in paracancerous tissues(29.7％)(x2=24.196,P＜0.001).The proportions of patients with TNM stage Ⅳ,serosal and extra-serosal infiltration,and lymph node metastasis in the high expression group were all higher than those in the low expression group(all P＜0.05).Among the 148 patients,44 developed immunotherapy resistance,and the resistance rate in the high expression group was higher than that in the low expression group[36.7％(33/90)vs 19.0％(11/58)](x2=5.290,P=0.021).ROC curve analysis showed that the area under the curve of STC2 expression level for predicting immunotherapy resistance in gastric cancer patients was 0.908(95％confidence interval:0.850-0.949),with a sensitivity of 81.82％and a specificity of 92.30％.Correlation heatmap analysis revealed that STC2 expression level in gastric cancer tissues was significantly negatively correlated with the infiltra-tion ratios of CD8+T cells,CD4+T cells and B cells as well as the positive rate of PD-1 in T cells(all P＜0.001),and significantly positively correlated with the infiltration ratios of FOXP3+Treg cells and CD68+macrophages as well as the positive rate of PD-L1 on the surface of tumor cells(all P＜0.001).Conclusion The expression level of STC2 is significantly elevated in gastric cancer tissues,which is associated with tumor invasion depth,lymph node metastasis and advanced clinical stage.Gastric cancer patients with high STC2 expression have a higher rate of immunotherapy resistance,and STC2 can serve as an effective biomarker for predicting immunotherapy resistance,whose mechanism may be related to the regulation of tumor immune microenvironment.