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Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H 2 O 2  → ‧OH for tumoral therapy. Unfortunately, H 2 O 2 is often taken from the limited endogenous supply of H 2 O 2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H 2 O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe 3+ -N ≡ C-Fe 2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O 2 , H 2 O 2, and ‧OH from H 2 O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments., (© 2023. Springer Nature Limited.)

Background: RNA-binding proteins (RBPs) are closely related to tumors, but little is known about the mechanism of RBPs in tumorigenesis and progression of gastric cancer (GC). As genes do not usually act alone in the pathway deregulation, gene pair combinations are more likely to become stable and accurate biomarkers. The purpose of our research is to establish a novel signature based on RBP gene pairs to predict the prognosis of gastric cancer patients., Methods: We downloaded genetic and clinical information from the TCGA and GEO database. TCGA and GSE13911 were used for screening differentially expressed genes (DEGs). The RBP genes were gathered from previous studies and employed to screen out DE-RBP genes after intersecting with DEGs. Samples were classified according to the relative expression of each pair of DE-RBP genes. The univariate Cox regression analysis and random forest were used to identify hub gene pairs to construct signature for predicting the prognosis of gastric cancer. Time-dependent ROC curves and KM survival curves were performed to evaluate the signature. GSEA was performed in TCGA training cohort and GSE62254 testing cohort to analyze enrichment pathways. Finally, the influence of these gene pairs on the prognosis of GC patients was further elucidated respectively through the combination of high and low expression of the two genes in each hub gene pair., Results: We screened out 6 hub RBP gene pairs (COL5A2/FEN1, POP1/GFRA1, EXO1/PLEKHS1, SLC39A10/CHI3L1, MMP7/PPP1R1 B and SLC5A6/BYSL) to predict the prognosis of patients with gastric cancer. Using the optimal cut-off value to divide patients into high-risk and low-risk groups in the training and testing cohort, we found that the overall survival (OS) of the low-risk group was higher than that of the high-risk group (P < 0.05). The area under the ROC curves for 1, 3, and 5 years were (0.659, 0.744, 0.758) and (0.624, 0.650, 0.653) in two cohorts. Univariate and multivariate Cox regression analysis showed that 6 RBP gene pairs signature were independent prognostic factors for gastric cancer (P < 0.05). In addition, the prognostic survival analysis showed that COL5A2-high/FEN1-low, POP1-low/GFRA1-high, EXO1-low/PLEKHS1-low,SLC39A10-high/CHI3L1-low, MMP7-high/PPP1R1 B-low, SLC5A6-low/BYSL-low had worse OS (P < 0.05). And the gene correlation analysis showed that there was no obvious correlation between the genes in each gene pairs except SLC5A6/BYSL and POP1/GFRA1. Finally, GSEA analysis showed that the high-risk group was enriched in tumor migration, invasion and growth-related pathways., Conclusion: Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Background: The clinicopathological features and prognosis of gastric signet ring cell carcinoma (GSRC) remain controversial, particularly with regard to sensitivity to postoperative adjuvant therapy., Aim: To compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes., Methods: By screening gastric cancer patients from 2010 to 2015 in the database of Surveillance, Epidemiology and End Results, and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University, we analyzed the general pathological characteristics of GSRC by the chi-square test. Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma. The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma. The prognosis model of advanced GSRC was established with R software, and the area under curve (AUC) and C-index were used to assess the accuracy of the model., Results: Analysis of pathological features revealed that signet ring-cell carcinoma (SRC) was more frequently seen in younger (< 60 years), female, and White patients compared to non-SRC patients. SRC was less commonly associated with early gastric cancer (EGC) (23.60% vs 39.10%), lower N0 (38.61% vs 61.03%), and larger tumour sizes > 5 cm (31.15% vs 27.10%) compared to the differentiated type, while the opposite was true compared to the undifferentiated type. Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients. In contrast, among advanced gastric cancer (AGC) patients, the prognosis of SRC patients was correlated with age, race, tumour size, AJCC stage, T-stage, and postoperative adjuvant therapy. The predictive model showed that the 3-year AUC was 0.787, 5-year AUC was 0.806, and C-index was 0.766. Compared to non-SRC patients, patients with SRC had a better prognosis in EGC [hazard ratio (HR): 0.626, 95% confidence interval (CI): 0.427-0.919, P < 0.05] and a worse prognosis in AGC (HR: 1.139, 95%CI: 1.030-1.258, P < 0.05). When non-SRC was divided into differentiated and undifferentiated types for comparison, it was found that in EGC, SRC had a better prognosis than differentiated and undifferentiated types, while there was no significant difference between differentiated and undifferentiated types. In AGC, there was no significant difference in prognosis between SRC and undifferentiated types, both of which were worse than differentiated types. A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival (34.6% and 36.2% vs 18.6%, P < 0.05)., Conclusion: The prognosis of SRC is better than that of undifferentiated type, especially in EGC, and its prognosis is even better than that of differentiated type. SRC patients can benefit from early detection, surgical resection, and aggressive adjuvant therapy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The interaction between hypoxia and RNA N6-methyladenosine (m6A) is an emerging focus of investigation. However, alterations in m6A modifications at distinct hypoxia levels remain uncharacterized in gastric cancer (GC). Unsupervised hierarchical clustering was performed to stratify samples into different clusters. Differentially expressed gene analysis, univariate Cox proportional hazards regression analysis, and hazard ratio calculations were used to establish an m6A score to quantify m6A regulator modification patterns. After using an algorithm integrating Least absolute shrinkage and selection operator (LASSO) and bootstrapping, we identified the best candidate predictive genes. Thence, we established an m6A-related hypoxia pathway gene prognostic signature and built a nomogram to evaluate its predictive ability. The area under the curve (AUC) value of the nomogram was 0.811, which was higher than that of the risk score (AUC=0.695) and stage (AUC=0.779), suggesting a high credibility of the nomogram. Furthermore, the clinical response of anti-PD-1/CTLA-4 immunotherapy between high- and low-risk patients showed a significant difference. Our study successfully explored a brand-new GC pathological classification based on hypoxia pathway genes and the quantification of m6A modification patterns. Comprehensive immune analysis and validation demonstrated that hypoxia clusters were reliable, and our signature could provide a new approach for clinical decision-making and immunotherapeutic strategies for GC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ning, Hu, Liu, Tian, Yu, Zhou, Li and Zong.)

Background: Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance. Accumulating evidence suggests that long non-coding ribonucleic acids (lncRNAs) are frequently aberrantly expressed in colorectal cancer (CRC)., Aim: To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC., Methods: We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups. Based on the Cox coefficient of the individual lncRNAs, we identified a nine-lncRNA signature that was associated with the survival of CRC patients in the training set ( n = 175). The prognostic value of this nine-lncRNA signature was validated in the testing set ( n = 174) and TCGA set ( n = 349). The prognostic models, consisting of these nine CRC-specific lncRNAs, performed well for risk stratification in the testing set and TCGA set. Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance., Results: Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival. Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC., Conclusion: A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC, thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)