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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 Ca 2+ 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., (© 2022. The Author(s).)

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer-related death worldwide. Aberrant protein translation contributes to the oncogenesis and development of cancers, and upregulation of translation initiation factor eIF4A1 has been observed in several kinds of malignancies. However, the role of eIF4A1 in gastric cancer progression remains unclear. In this study, we found that the expression of eIF4A1, a component of translation initiation complex, was increased in gastric cancer. High expression of eIF4A1 was positively associated with poor tumor differentiation, late T stage, lymph node metastasis, advanced TNM stage, and poor prognosis in patients with gastric cancer. Overexpression of eIF4A1 promoted the migration and invasion of gastric cancer cells in vitro and enhanced tumor metastasis in nude mice model. Mechanism studies revealed that eIF4A1 induced epithelial-to-mesenchymal transition (EMT) of gastric cancer cells through driving the translation of SNAI1 mRNA. Together, these findings indicate that eIF4A1 promotes EMT and metastasis of gastric cancer and suggest that eIF4A1 is a potential target for the adjuvant therapy for gastric cancer patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a key effector in the activation of nuclear factor kappa B (NF-κB). Nevertheless, the role of TRAF2 in gastric tumorigenesis remains little defined., Methods: Immunohistochemistry was used to find the relationship between TRAF2 expression and clinicopathological characteristics of gastric cancer patients, and nomogram was applied to predict the overall survival of patients. Besides, we performed transwell assays to detect the function of TRAF2 in promoting metastasis and explored the correlations between TRAF2, NF-κB, and interleukin-8 (IL-8) in vitro. In addition, we examined the correlation between TRAF2 and tumor microenvironment by immunohistochemistry staining., Results: In our study, we found that TRAF2 expression was markedly increased in gastric cancer tissues. High intratumoral TRAF2 staining, which was associated with tumor invasion and metastasis, was also an independent poor prognosticator for gastric cancer patients. In vitro studies revealed that TRAF2 enhanced NF-κB activation and subsequent IL-8 expression in gastric cancer cells. Inhibition of NF-κB or IL-8 signaling attenuated TRAF2-induced migration and invasion abilities. High TRAF2 expression was confirmed to be associated with both high intratumoral and serum levels of IL-8. In addition, TRAF2 expression was positively correlated with neutrophil and macrophage infiltration as well as microvessels formation in gastric cancer samples., Conclusions: These results suggest that TRAF2 functions as an important modulator in tumor metastasis and tumor microenvironment formation and is a novel independent prognostic factor of gastric cancer., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the features of clinicopathology and prognosis in young gastric cancer patients., Methods: Clinicopathological data of 90 young gastric cancer patients (≤40 years old) who received radical gastrectomy in the Department of General Surgery of Zhongshan Hospital, Fudan University from January 2013 to December 2014 were retrospectively analyzed. Survival data were obtained by follow-up and the last follow-up time was October 2016. Log-rank test and Cox regression model were used to analyze the risk factors of prognosis and these factors included gender, age, tumor size, degree of differentiation, histological type, Lauren pattern, T stage, N stage, vessel carcinoma embolus, clinical symptom, anemic condition, CA19-9 level, et al., Results: The median age of 90 patients was 35 years old, of whom, 20(22.2%) patients were ≤30 years old and 70(77.8%) patients were between 31 and 40 years old. There were 70(77.8%) female patients, 38(42.2%) patients with anemia, 11(12.8%) patients with elevated CA19-9 level and 9(10.0%) patients with family history of gastrointestinal tumors. The mean time of all the patients from presence of symptom to consultation was 8.2 months. Postoperative pathology revealed 65(72.2%) patients with poorly differentiated adenocarcinoma, 6(6.7%) patients with mucinous adenocarcinoma, 9(10%) patients with signet-ring cell carcinoma, and 10(11.1%) patients with papillary-canalicular adencarcinoma. Sixty-nine (76.7%) patients were diagnosed as advanced gastric cancer and 67(74.4%) patients were involved with lymphatic metastasis when they visited our hospital. Univariate analysis showed that gender (P=0.021), tumor size (P=0.001), depth of tumor infiltration (P=0.016), lymphatic metastasis (P=0.000), vessel carcinoma embolus (P=0.001), elevated CA19-9 level (P=0.001), and anemia (0.024) were statistically related with postoperative survival. Multivariate analysis showed that lymphatic metastasis was an independent risk factor of the poor prognosis of young patients (HR:2.774, 95%CI:1.435 to 5.364, P=0.002)., Conclusions: The majority of young gastric cancer cases are female with poorly differentiated adenocarcinoma. Most patients are diagnosed as advanced gastric cancer with lymphatic metastasis when they visit hospital at the first time. The lymphatic metastasis is an independent risk factor of prognosis in young gastric cancer patients.

Background: 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., Methods: 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., Results: 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., Conclusions: The IGCA staging system can stratify stage III gastric cancer patients more properly than the AJCC7 system.

Postoperative complications after gastric cancer surgery has their own specificity and complexity, and the strategies for prevention and treatment should be of equal emphasis on both theory and technology. Based on the knowledge and familiarity with different postoperative complications, to efficiently prevent them, it is not only necessary to strengthen the training of acknowledged operative strategy, smooth and precise surgical techniques, but also to address the importance of overall preoperative assessment for patients, to treat the basic diseases, and to improve and correct their general conditions. Combining with the concept and basic protocol of enhanced recovery after surgery (ERAS), it is preferred to work out an individualized perioperative preventing strategy for patients who have high risk factors of specific postoperative complications. After the operation, to guarantee intensive and individual managements for patients, to catch early abnormal signs, then to make early and precise diagnosis, and to do timely response and accurate treatments, including timely and proper re-operations, can improve the efficacy of complications and promote the recovery of patients as soon as possible.

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., Competing Interests: The authors declare no competing financial interests.

Gastric cancer remains the third leading cause of cancer-related mortality worldwide, and invasion and metastasis of gastric cancer represent the major reason for its poor prognosis. Glutamine: fructose-6-phosphate amidotransferase 1 (GFAT1) is the first and rate-limiting enzyme of hexosamine biosynthesis pathway (HBP). Nevertheless, the role of GFAT1 in gastric cancer is little investigated. In this study, we found that the expression of GFAT1 was decreased in gastric cancer. Low expression of GFAT1 was positively associated with vessel invasion, late T stage, lymph node metastasis, distant metastasis, advanced TNM stage and poor prognosis in patients with gastric cancer. Furthermore, in vitro and in vivo studies revealed that down-regulation of GFAT1 promoted epithelial-to-mesenchymal transition (EMT) and invasive activities in gastric cancer cells through inducing the expression of TGF-β1. The GFAT1 expression also significantly correlated with EMT-related factors in gastric cancer patients. Together, these findings indicate that GFAT1 functions as a novel suppressor of EMT and tumor metastasis in gastric cancer., Competing Interests: The authors declare no competing interests.

The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12(+) endothelial cells and Cxcr4(+) gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche., (Copyright © 2015 Elsevier Inc. All rights reserved.)