Trophinin-associated protein (TROAP) is a cytoplasmic protein required for microtubular cytoskeleton regulation and spindle assembly, and its expression plays a critical role in the initiation and progression of various types of cancer. However, little is known about the role of TROAP in breast cancer (BC). TROAP mRNA expression levels and clinical data from Gene Expression Omnibus (GEO) datasets (GSE42568, 104 BC patients; GSE1456, 159 BC patients; and GSE21653, 266 BC patients) were analyzed by the R2: Genomics Analysis and Visualization Platform to estimate overall survival (OS). We also analyzed the genes correlated with TROAP by gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict potential relationships between TROAP and other genes in BC. Our study verified that both TROAP mRNA and protein expression levels were upregulated in human BC samples and cell lines. In vitro experiments demonstrated that TROAP knockdown significantly inhibited cell proliferation, the G1 to S phase transition, and the migration and invasion abilities of BC cells. The present study suggests that TROAP plays an important role in promoting the proliferation, invasion, and metastasis of BC.

Copper is an essential cofactor for all organisms. However, it can become toxic if its concentration rises above a specific level. This level is controlled by evolutionary conserved homeostatic mechanisms. Recently, a new type of cell death called cuproptosis has been found. The process represents a copper-dependent, regulated form of cell death that is distinct from all known death mechanisms and relies on mitochondrial respiration. The mechanism of cuproptosis involves the direct binding of copper to lipidated parts in the tricarboxylic acid (TCA) cycle. This results in the abnormal aggregation of lipoylated proteins and the destabilization of iron-sulfur cluster (Fe-S) proteins. These events induce proteotoxic stress, ultimately leading to cell death. Copper-induced cell death is controlled by proteolipid acylation, which is mediated by the mitochondrial iron-sulfur protein FDX1. Copper overload also inhibits the biosynthesis of iron-sulfur (Fe-S) clusters and impairs the activity of Fe-S enzymes. As a result, mitochondrial function is disrupted. Both copper-induced cell death and impaired copper homeostasis arise from the same mechanistic basis. The expression of copper import gene SLC31A1 (CTR1) and export genes ATP7A and ATP7B significantly influences cuproptosis. The tumor suppressor p53 may participate in this process by modulating glycolysis and mitochondrial metabolism. In contrast, glutathione (GSH) reduces copper ion cytotoxicity by binding copper to form a complex. The growth and spread of tumor cells is more dependent on copper than that of normal cells.The copper ionophore elesclomol (ES) kills cancer cells by transporting copper ions into them. This ES-Cu complex not only inhibits cancer cell proliferation but also activates an immune response. Moreover, when ES is combined with αPD-L1, it might increase the effectiveness of cancer treatment. This gives a new idea for treating cancer.

Glutamine fructose‐6‐phosphate aminotransferase 2 (GFPT2) is a rate‐limiting enzyme in hexosamine biosynthesis involved in the occurrence and progress of many cancers. What role it plays in gastric cancer (GC) is still unclear. In this study, transcriptome sequencing data from the Harbin Medical University (HMU)‐GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined with the HMU‐TCGA training cohort to analyze the biological function and clinical significance of GFPT2. The correlation of GFPT2 with immune cells and stromal cells was analyzed in the GC immune microenvironment through transcriptome sequencing data and a public single‐cell sequencing database. In cell lines, GC tissues, and the tissue microarray, GFPT2 protein expression was confirmed by western blotting and immunohistochemistry. The mRNA of GFPT2 was highly expressed in the tumor (p < 0.001), and GC cells and tumors expressed high levels of GFPT2 protein. Compared to low expression, high GFPT2 mRNA expression was associated with higher levels of tumor invasion, higher pathological stages, and poor prognosis (p = 0.02) in GC patients. In a drug susceptibility analysis, GFPT2 mRNA expression was associated with multiple chemotherapeutic drug sensitivity, including docetaxel, paclitaxel, and cisplatin. Gene enrichment analysis found that GFPT2 was mainly primarily involved in the extracellular matrix receptor interaction pathway. The ESTIMATE, CIBERSORT, and ssGSEA algorithms showed that GFPT2 was associated with immune cell infiltration. In addition, GFPT2 was more likely to be expressed within cancer‐associated fibroblasts (CAFs), and high levels of GFPT2 expression were highly correlated with four CAFs scores (all p < 0.05). Finally, a prognostic model to assess the risk of death in GC patients was constructed based on GFPT2 protein expression and lymph node metastasis rate. In conclusion, GFPT2 plays an essential role in the function of CAFs in GC. It can be used as a biomarker to assess GC prognosis and immune infiltration.

Serum CD4, CD8, and CD19 are markers of systemic inflammation. However, there is little evidence on the influence of inflammation on the tumor microenvironment and the prognostic indicators of gastric cancer (GC). In this study, two hundred and eight patients who underwent radical gastrectomy for GC were included. Preoperative peripheral blood samples were used to analyze Serum CD4, CD8, and CD19. The optimal cutoff levels for CD4, CD8, and CD19 were defined by receiver operating characteristic curve analysis (%, %, and %). The areas with specific CD4⁺T cells, CD8⁺T cells, and CD19⁺B cells within the tumor microenvironment were measured in paraffin sections by immunohistochemistry and analyzed by Image-Pro Plus. 94 patients had low CD4, and 124 patients had high CD4 levels. 31 patients had low CD8, and 187 patients had high CD8 levels. 64 patients had low CD19, and 154 patients had high CD19 levels. Infiltration of CD4⁺T cells was associated with serum CD4 ( ). Serum CD4 and CD19 and the infiltration of CD4⁺T cells, CD8⁺T cells, and CD19⁺B cells were significant in predicting the prognosis of GC. Low CD4 level, infiltration of CD8⁺T cells, and high infiltration of CD4⁺T cells and CD19⁺B cells were correlated with worse overall survival in multivariate analysis. Collectively, our results provide evidence that serum CD4 is associated with the infiltration of CD4⁺T cells in the tumor microenvironment, which indicates the prognostic value of systemic inflammation in GC.

Abnormal FBLN5 expression levels are related to various cancer types. This study is the first to explore its clinical and biological significances in gastric cancer (GC). We used The Cancer Genome Atlas-GC (TCGA-GC) and Gene Expression Omnibus (GEO) databases to identify the differential expression of FBLN5, and its association with clinical pathological characteristics was analyzed. A Kaplan–Meier plotter was used to calculate the impact of FBLN5 on GC patient prognosis, and the biological functions of FBLN5 were analyzed. In addition, we constructed a GC tissue microarray, and performed an immunohistochemical staining of FBLN5 to verify our findings. Western blotting was conducted simultaneously to confirm that FBLN5 was overexpressed in GC. We found that the high level of FBLN5 mRNA in GC was associated with a poor prognosis. High FBLN5 expression levels were significantly correlated with INFc and N3 lymph node metastasis. Univariate and multivariate analyses showed that FBLN5 expression levels and lymph node metastasis rate were independent risk factors related to GC patient prognosis, which can be combined to construct a nomogram to serve patients. Therefore, we believe that FBLN5 is significantly related to the poor prognosis of GC patients. FBLN5 is a valuable prognostic indicator to evaluate the prognosis of GC.

Gastric cancer (GC) might have significantly different outcomes within the same AJCC/UICC-TNM stage. The purpose of this study is to help predict the different prognosis through the pattern of immune cell infiltration. We retrospectively analyzed 2605 patients who underwent radical gastrectomy in the Harbin Medical University Cancer Hospital between 2002 and 2013. For stage III with significantly different survival probability, we analyzed the relationship between immune cell surface antigen and survival in TCGA dataset. Furthermore, 200 cases in stage III GC with different survival outcomes were randomly selected for immunohistochemical verification. Image Plus software was used to evaluate the area of immune cell infiltration. We found that patients in stage III had significantly different outcomes. Bioinformatics analysis showed that there was a significant negative correlation between the expression of immune cell surface antigen and prognosis. In order to investigate whether immune infiltration can distinguish GC patients in stage III with differences in prognosis, we verified by immunohistochemistry that CD4⁺ T cells, CD20⁺ B cells, and CD177⁺ neutrophils infiltrated more in group B with better prognosis; CD8⁺ T cells, CD68⁺ macrophages, and CD117⁺ mast cells infiltrated more in group A with poor prognosis. CD117⁺ mast cells have the same trend of predicting significance for prognosis in the RNA and protein levels. In conclusion, patients with GC in northeastern China have significant prognostic differences only in stage III. CD117⁺ mast cells may be important evaluation factors in further studies of Immunoscore.