STING (stimulator of interferon genes) has recently been found to play an important role in host defenses against virus and intracellular bacteria via the regulation of type-I IFN signaling and innate immunity. Chronic infection with Helicobacter pylori is identified as the strongest risk factor for gastric cancer. Thus, we aim to explore the function of STING signaling in the development of gastric cancer. Immunohistochemistry was used to detect STING expression in 217 gastric cancer patients who underwent surgical resection. STING protein expression was remarkably decreased in tumor tissues compared to non-tumor tissues, and low STING staining intensity was positively correlated with tumor size, tumor invasion depth, lymph mode metastasis, TNM stage, and reduced patients’ survival. Multivariate analysis identified STING as an independent prognostic factor, which could improve the predictive accuracy for overall survival when incorporated into TNM staging system. In vitro studies revealed that knock-down of STING promoted colony formation, viability, migration and invasion of gastric cancer cells, and also led to a defect in cytosolic DNA sensing. Besides, chronic H. pylori infection up-regulated STING expression and activated STING signaling in mice. In conclusion, STING was proposed as a novel independent prognostic factor and potential immunotherapeutic target for gastric cancer.

A new staging system recently proposed by the IGCA has demonstrated a better capacity of stratifying different prognoses for gastric cancer than the 7th edition AJCC staging system (AJCC7). The aim of this study was to evaluate the efficacy of the IGCA system in Chinese patients. Medical records of patients with gastric cancer who received curative surgery in our center from January 2003 to December 2011 were reviewed retrospectively. All the lesions were staged according to both AJCC7 and IGCA staging systems. Overall survival (OS) of the patients was used as the observation endpoint. One thousand five hundred twenty-six cases were included in this study. By comparing the AJCC7 system with the IGCA systems, 395 cases were stratified into different stages, most of which were in stage III. The IGCA system could better stratify stage IIIB and IIIC patients (5-year OS, 38.1% vs. 29.0%; P = 0.005) than the AJCC7 system (5-year OS, 38.2% vs. 35.9%; P = 0.148). T3N3bM0, T4aN2M0 and T4aN3bM0 made up 97.5% (385/395) of the stage shift. T3N3bM0, which was stratified to stage IIIB in the AJCC7 system, showed a significant poorer prognosis than T4aN2M0 and T4aN3aM0, which were staged to IIIB and IIIC in the same system. The improper staging was revised in the IGCA staging system. The IGCA staging system can stratify stage III gastric cancer patients more properly than the AJCC7 system.

Gastric cancer ranks fourth for mortality globally among various malignant tumours, and invasion and metastasis are the major reason leading to its poor prognosis. Recently, accumulating studies revealed the role of reticulon proteins in cell growth and transmigration. However, the expression and biological function of reticulon proteins in human gastric cancer remain largely unclear. Herein, we explored the potential role of reticulon 2 (RTN2) in the progression of gastric cancer. Tissue microarray was used to determine the expression levels of RTN2 in 267 gastric cancer patients by immunohistochemistry. Gastric cancer cell lines were utilised to examine the influences of RTN2 on cellular migration and invasion abilities, epithelial-to-mesenchymal transition (EMT) and signalling pathway. In vivo studies were also performed to detect the effect of RTN2 on tumour metastasis. We found that RTN2 expression was notably upregulated in tumour tissues compared to pericarcinomatous tissues. High RTN2 expression was positively correlated with patients’ age, vessel invasion, tumour invasion depth, lymph node metastasis and TNM stage. Besides, high RTN2 staining intensity was associated with adverse survival which was further identified as an independent prognostic factor for gastric cancer patients by multivariate analysis. And the predictive accuracy was also improved when incorporated RTN2 into the TNM-staging system. RTN2 could promote the proliferation, migration and invasion of gastric cancer cells in vitro and lung metastasis in vivo. Mechanistically, RTN2 interacted with IP3R, and activated ERK signalling pathway via facilitating Ca²⁺ release from the endoplasmic reticulum, and subsequently drove EMT in gastric cancer cells. These results proposed RTN2 as a novel promotor and potential molecular target for gastric cancer therapies.

Background: This study aimed to investigate the clinical and prognostic significance of preoperative maximum standardized uptake value (SUVmax) and GLUT-1 expression in patients with advanced gastric cancer (AGC). Methods: Medical records of patients who were diagnosed with AGC between 2018 and 2020 at Zhongshan Hospital of Fudan University (Shanghai, China) were retrospectively analyzed. Finally, 182 patients were enrolled, and for each patient, SUVmax was calculated for the primary lesion on PET/CT prior to curative surgery. A total of 165 clinical tissue specimens were collected for immunohistochemical analysis of GLUT-1 expression. Results: A total of 182 patients were divided into two groups based on their SUVmax values. The low SUVmax group comprised 92 patients. Patients with low SUVmax tended to be younger and included a higher proportion of women, with their primary tumors typically smaller or in earlier TNM stages. The median follow-up time was 52 months. The 1-, 3-, and 5-year progression-free survival (PFS) rates were 90.7%, 71.4%, and 67.0%, respectively. Among them, 33 patients experienced recurrence and metastasis, and 40 ultimately died. Log-rank analysis revealed that the low SUVmax group exhibited superior progression-free survival (PFS) and overall survival (OS). Multivariate analysis indicated that, for AGC without preoperative treatment, later stage (stage III) was independently correlated with a higher risk of recurrence (HR = 3.049; 95%CI = 1.076–8.639; p = 0.036), while the low SUVmax group exhibited a reduced risk of recurrence and mortality compared with the high SUVmax group (HR = 0.565; 95%CI = 0.326–0.979; p = 0.042). Conclusions: The clinicopathological characteristics of patients with AGC with different SUVmax values appeared significantly different. Tumor stage and SUVmax were found as independent factors affecting postoperative recurrence and death of patients with AGC.