Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment.

Fiber sheath interaction protein 1 (FSIP1) plays a crucial role in cancer development and occurrence, but its influence on gastric cancer is still unclear. In this study, differential mRNA analysis was performed by TCGA database for the Limma analysis algorithm, and the gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and the gene set enrichment analysis (GSEA) were used for bioinformatics functional enrichment analysis. A gastric cancer cell model with FSIP1 mRNA knockdown was constructed by RNA interference. Cell counting kit-8 and transwell migration/invasion assay were performed to verify the cell function, and western blotting was employed to confirm the expression of target genes. The GSEA analysis revealed that FSIP1 was associated with epithelial-mesenchymal transition (EMT). The high expression group also had a significant positive correlation with the markers of fibroblast in tumor microenvironment (TME). Western blotting showed that FSIP1 was generally upregulated in gastric cancer cell lines. FSIP1 mRNA knockdown cell lines inhibited gastric cells proliferation, migration, and metastasis in vitro, and the protein levels of EMT-related markers N-cadherin and vimentin were reduced. Our work proved that FSIP1 promoted EMT by regulating fibroblasts in the TME, thereby promoting the carcinogenic activity of cancer cells in proliferation, invasion, and migration. FSIP1 may take a role of the occurrence and could be a potential therapeutic target and offer a new insight into the underlying mechanism of gastric cancer.

A prognostic marker LTBP1 is associated with epithelial mesenchymal transition and can promote the progression of gastric cancer.

LTBP1 is closely related to TGF-ß1 function as an essential component, which was unclear in gastric cancer (GC). Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined to form a training cohort to calculate the connection between LTBP1 mRNA expression, prognosis and clinicopathological features. The training cohort was also used to verify the biological function of LTBP1 and its relationship with immune microenvironment and chemosensitivity. In the tissue microarrays (TMAs), immunohistochemical (IHC) staining was performed to observe LTBP1 protein expression. The correlation between LTBP1 protein expression level and prognosis was also analyzed, and a nomogram model was constructed. Western blotting (WB) was used in cell lines to assess LTBP1 expression. Transwell assays and CCK-8 were employed to assess LTBP1's biological roles. In compared to normal gastric tissues, LTBP1 expression was upregulated in GC tissues, and high expression was linked to a bad prognosis for GC patients. Based on a gene enrichment analysis, LTBP1 was primarily enriched in the TGF-ß and EMT signaling pathways. Furthermore, high expression of LTBP1 in the tumor microenvironment was positively correlated with an immunosuppressive response. We also found that LTBP1 expression (p = 0.006) and metastatic lymph node ratio (p = 0.044) were independent prognostic risk factors for GC patients. The prognostic model combining LTBP1 expression and lymph node metastasis ratio reliably predicted the prognosis of GC patients. In vitro proliferation and invasion of MKN-45 GC cells were inhibited and their viability was decreased by LTBP1 knockout. LTBP1 plays an essential role in the development and progression of GC, and is a potential prognostic biomarker and therapeutic target for GC.

Cancer-associated fibroblast expression of glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a prognostic marker in gastric 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.

Clinical and Biological Significances of FBLN5 in Gastric Cancer.

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.

The prognostic marker elastin correlates with epithelial-mesenchymal transition and vimentin-positive fibroblasts in gastric cancer.

Elastin (ELN) fibers are essential constituents of the tumor microenvironment of gastric cancer (GC). However, few studies have investigated the clinical prognostic significance of ELN in GC. We screened for molecular markers that were highly related to distant metastasis by transcriptome sequencing. The Cancer Genome Atlas (TCGA) and Harbin Medical University (HMU) validation cohorts were used to validate ELN expression and to explore molecular mechanisms. Immunohistochemistry for ELN, vimentin (VIM), and fibroblast activation protein, and elastic fiber-specific staining were used to evaluate the relationship between ELN and prognosis. R studio was used to construct a nomogram prognostic model. In this study, we found that ELN mRNA levels were significantly higher in cancer tissues and were associated with poor prognosis in TCGA and HMU patients. Gene set enrichment analysis showed that ELN was mainly enriched in the epithelial-mesenchymal transition (EMT) pathway. The mRNA expression of ELN was positively correlated with fibroblast molecular markers, especially VIM. For validation, we collected a tissue microarray containing 180 pairs of samples. We found that ELN was positively correlated with VIM expression in cancer tissue but not in paracancerous tissues by immunohistochemistry staining. Univariate and multivariate analyses showed that the expression of ELN and lymph node metastasis rate were independent predictors for overall survival. Moreover, a nomogram model was used to evaluate the risk of death by combining the expression of ELN and lymph node metastasis rate. ELN may play an important role in the progression of GC by regulating EMT and is a useful prognostic indicator in predicting the prognosis of GC.

Roles of platelets in tumor invasion and metastasis: A review.

The invasion and metastasis of malignant tumors are major causes of death. The most common metastases of cancer are lymphatic metastasis and hematogenous metastasis. Hematogenous metastasis often leads to rapid tumor dissemination. The mechanism of hematogenous metastasis of malignant tumors is very complex. Some experts have found that platelets play an important role in promoting tumor hematogenous metastasis. Platelets may be involved in many processes, such as promoting tumor cell survival, helping tumor cells escape immune surveillance, helping tumors attach to endothelial cells and penetrating capillaries for distant metastasis. However, recent studies have shown that platelets can also inhibit tumor metastasis. At present, the function of platelets in tumor progression has been widely studied, and they not only promote tumor cell metastasis, but also have an inhibitory effect. Therefore, in-depth and summary research of the molecular mechanism of platelets in tumor cell metastasis is of great significance for the screening and treatment of cancer patients. The following is a brief review of the role of platelets in the process of malignant tumor metastasis.