CREM Is Correlated With Immune-Suppressive Microenvironment and Predicts Poor Prognosis in Gastric Adenocarcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Yu K
PROVIDER: S-EPMC8685542 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundGlioma is the most malignant cancer in the brain. As a major vitamin-K-dependent protein in the central nervous system, PROS1 not only plays a vital role in blood coagulation, and some studies have found that it was associated with tumor immune infiltration. However, the prognostic significance of PROS1 in glioma and the underlying mechanism of PROS1 in shaping the tumor immune microenvironment (TIME) remains unclear.MethodsThe raw data (including RNA-seq, sgRNA-seq, clinicopathological variables and prognosis, and survival data) were acquired from public databases, including TCGA, GEPIA, CGGA, TIMER, GEO, UALCAN, and CancerSEA. GO enrichment and KEGG pathway analyses were performed using "cluster profiler" package and visualized by the "ggplot2" package. GSEA was conducted using R package "cluster profiler". Tumor immune estimation resource (TIMER) and spearman correlation analysis were applied to evaluate the associations between infiltration levels of immune cells and the expression of PROS1. qRT-PCR and WB were used to assay the expression of PROS1. Wound-healing assay, transwell chambers assays, and CCK-8 assays, were performed to assess migration and proliferation. ROC and KM curves were constructed to determine prognostic significance of PROS1 in glioma.ResultsThe level of PROS1 expression was significantly increased in glioma in comparison to normal tissue, which was further certificated by qRT-PCR and WB in LN-229 and U-87MG glioma cells. High expression of PROS1 positively correlated with inflammation, EMT, and invasion identified by CancerSEA, which was also proved by downregulation of PROS1 could suppress cells migration, and proliferation in LN-229 and U-87MG glioma cells. GO and KEGG analysis suggested that PROS1 was involved in disease of immune system and T cell antigen receptor pathway. Immune cell infiltration analysis showed that expression of PROS1 was negatively associated with pDC and NK CD56 bright cells while positively correlated with Macrophages, Neutrophils in glioma. Immune and stromal scores analysis indicated that PROS1 was positively associated with immune score. The high level of PROS1 resulted in an immune suppressive TIME via the recruitment of immunosuppressive molecules. In addition, Increased expression of PROS1 was correlated with T-cell exhaustion, M2 polarization, poor Overall-Survival (OS) in glioma. And it was significantly related to tumor histological level, age, primary therapy outcome. The results of our experiment and various bioinformatics approaches validated that PROS1 was a valuable poor prognostic marker.ConclusionIncreased expression of PROS1 was correlated with malignant phenotype and associated with poor prognosis in glioma. Besides, PROS1 could be a possible biomarker and potential immunotherapeutic target through promoting the glioma immunosuppressive microenvironment and inducing tumor-associated macrophages M2 polarization.
| S-EPMC9845921 | biostudies-literature
Project description:Tubulin epsilon and delta complex 2 (TEDC2) is a protein coding gene whose functions are poorly identified yet. This study aimed to identify the role of TEDC2 in prognosis and immune microenvironment of lung adenocarcinoma (LUAD). Through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, the mRNA expression of TEDC2 was upregulated in LUAD tissues compared to normal tissues. The protein level of TEDC2 was also higher in LUAD in the Human Protein Atlas. The receiver operating characteristic (ROC) curve showed that high TEDC2 level could distinguish LUAD patients from normal subjects. In addition, the impact of TEDC2 expression on prognosis was evaluated by Kaplan-Meier and Cox regression analyses, and the results suggested that high TEDC2 expression was significantly associated with poor prognosis and was the independent prognostic factor in LUAD. GO and KEGG pathway analyses indicated the co-expressed genes of TEDC2 were mainly related to mitotic cell cycle processes. Importantly, high expression of TEDC2 indicated low infiltration of immune cells, especially dendritic cells and B cells. TEDC2 was also positively correlated with immune checkpoints such as PDCD1, LAG3 and CD276. Taken together, this study preliminarily revealed the clinical significance of TEDC2 in LUAD and provided novel insights into the role of TEDC2 in immune microenvironment.
| S-EPMC10042817 | biostudies-literature
Project description:Background: C-X-C motif chemokine 5 (CXCL5) is an important attractant for immune cell accumulation in tumor tissues. Recent evidence has shown that CXCL5 could promote carcinogenesis and cancer progression in a variety of cancer types. However, the relationships between CXCL5, immune cell infiltration and pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. This study aimed to explore the role and regulative mechanism of CXCL5 in PDAC carcinogenesis. Materials and Methods: The expression of CXCL5 in PDAC was analyzed based on online databases and tissue microarray staining, and Western blotting of CXCL5 in PDAC cell lines and patient samples. The correlation between CXCL5 expression and clinicopathological features, prognosis and immune cell infiltration in tumor tissues was analyzed. Results: High expression of CXCL5 was observed both in PDAC tumor tissue and PDAC cell lines, compared to normal pancreas tissues and normal ductal epithelium cells. High CXCL5 expression in tumor tissues was positively correlated with an advanced T stage (p=0.036), a positive tumor lymph node metastasis (p=0.014), a poor differentiation status (p=0.003) and a poor prognosis (p=0.001). Combination of CA242 and CXCL5 expression (p<0.0001) served as a better prognostic factor than CA242 alone (p=0.006). In addition, PDAC patients with high CXCL5 expression had more intratumoral M2 polarized macrophages (p=0.0248), neutrophils (p=0.0068) and IgG+ plasma cells (p=0.0133) than patients with low CXCL5 expression. Conclusions: The expression of CXCL5 is elevated in pancreatic cancer cells. High CXCL5 expression is positively correlated with poor survival and the increased infiltration of several types of immune suppressive cells. Thus, CXCL5 could be a promising therapeutic target for PDAC immunotherapy.
| S-EPMC7065995 | biostudies-literature
Project description:BackgroundDisulfidptosis is a newly identified mechanism of cell death triggered by disulfide stress. Thus, gaining a comprehensive understanding of the disulfidptosis signature present in gastric cancer (GC) could greatly enhance the development of personalized treatment strategies for this disease.MethodsWe employed consensus clustering to identify various subtypes of disulfidptosis and examined the distinct tumor microenvironment (TME) associated with each subtype. The Disulfidptosis (Dis) score was used to quantify the subtype of disulfidptosis in each patient. Subsequently, we assessed the predictive value of Dis score in terms of GC prognosis and immune efficacy. Finally, we conducted in vitro experiments to explore the impact of Collagen X (COL10A1) on the progression of GC.ResultsTwo disulfidptosis-associated molecular subtypes (Discluster A and B) were identified, each with distinct prognosis, tumor microenvironment (TME), immune cell infiltration, and biological pathways. Discluster A, characterized by high expression of disulfidptosis genes, exhibited a high immune score but poor prognosis. Furthermore, the Dis score proved useful in predicting the prognosis and immune response in GC patients. Those in the low Dis score group showed better prognosis and increased sensitivity to immunotherapy. Finally, our experimental findings validated that downregulation of COL10A1 expression attenuates the proliferation and migration capabilities of GC cells while promoting apoptosis.ConclusionsThis study demonstrates that the disulfidptosis signature can assist in risk stratification and personalized treatment for patients with GC. The results offer valuable theoretical support for anti-tumor strategies.
| S-EPMC11325698 | biostudies-literature
Project description:Gliomas are the most common and lethal primary malignant tumor of the brain. Routine treatment including surgical resection, chemotherapy, and radiotherapy produced limited therapeutic effect, while immunotherapy targeting the glioma microenvironment has offered a novel therapeutic option. PDIA5 protein is the member of PDI family, which is highly expressed in glioma and participates in glioma progression. Based on large-scale bioinformatics analysis, we discovered that PDIA5 expression level is upregulated in aggressive gliomas, with high PDIA5 expression predicting poor clinical outcomes. We also observed positive correlation between PDIA5 and immune infiltrating cells, immune related pathways, inflammatory activities, and other immune checkpoint members. Patients with high PDIA5 high-expression benefited from immunotherapies. Additionally, immunohistochemistry revealed that PDIA5 and macrophage biomarker CD68 were upregulated in high-grade gliomas, and patients with low PDIA5 level experienced favorable outcomes among 33 glioma patients. Single cell RNA sequencing exhibited that PDIA5 was in high level presenting in neoplastic cells and macrophages. Cell transfection and co-culture of glioma cells and macrophages revealed that PDIA5 in tumor cells mediated macrophages exhausting. Altogether, our findings indicate that PDIA5 overexpression is associated with immune infiltration in gliomas, and may be a promising therapeutic target for glioma immunotherapy.
| S-EPMC7921737 | biostudies-literature
Project description:Long non-coding RNA PMS1 homolog 2 mismatch repair system component pseudogene 2 (PMS2L2) is a key player in lipopolysaccharide-induced inflammatory responses. Preliminary deep sequencing data revealed that PMS2L2 was downregulated in gastric adenocarcinoma (GA) tissues compared with healthy adjacent tissues and the aim of the present study was to investigate the role of PMS2L2 in GA. In the present study, reverse transcription-quantitative PCR assays were performed to analyze gene expression. Cell transfections were performed to analyze gene interactions and Transwell assays were performed to analyze cell invasion and migration. The results revealed that PMS2L2 expression was downregulated in cancer tissues obtained from patients with GA compared with healthy adjacent tissues and was not significantly affected by clinical stage. Furthermore, low levels of PMS2L2 in cancer tissues were closely associated with a low overall 5-year survival rate in patients. MicroRNA (miR)-25 was upregulated in GA tissues compared with healthy adjacent tissues and inversely associated with PMS2L2 levels. In GA cells in vitro, overexpression of PMS2L2 downregulated the expression of miR-25, while miR-25 overexpression did not significantly affect PMS2L2 expression. Furthermore, PMS2L2 overexpression inhibited the migration and invasion of GA cells. miR-25 overexpression partially rescued the decreased migration and invasion of GA cells caused by PMS2L2 overexpression. Therefore, PMS2L2 may downregulate miR-25 expression to inhibit GA.
| S-EPMC7285845 | biostudies-literature
Project description:BackgroundsThe deubiquitinating enzyme OTUB1 participates in multiple cellular processes. However, its expression and functions in gastric adenocarcinoma remains unknown. The aim of this study was to investigate the expression of OTUB1 and its biological role in gastric adenocarcinoma.MethodsWe used immunohistochemistry to analyze OTUB1 expressions levels in 80 paired samples of gastric adenocarcinoma and adjacent normal tissue (ANT) and 30 samples of intraepithelial neoplasia (IN). We also analyzed the correlation between OTUB1 expression and clinicopathological parameters and patient survival status. Moreover, we performed wound-healing, transwell, RT-qPCR and Western blot assays to evaluate the impact of OTUB1 on tumor migration and invasion.ResultsIn gastric adenocarcinomas, staining for OTUB1 was localized in the cytoplasm. The proportion of samples that expressed OTUB1 and the intensity of its expression were much higher in gastric adenocarcinoma tissues (61 out of 80, 76.25%) than that in either IN (10 out of 30, 33.33%, p<0.001) or ANT (7 out of 80, 8.75%, p<0.001) samples. In malignant cases, higher expression OTUB1 levels were significantly associated with deeper tumor invasion depths (p=0.02), advanced lymph node status (p=0.008) and TNM stage (p=0.001), lymph duct invasion (p<0.001) and nerve invasion (p=0.013). Univariate and multivariate Cox regression analyses revealed that OTUB1 was an independent risk factor for disease-specific survival but not disease-free survival. In vitro wound-healing and transwell assays showed that OTUB1 overexpression promoted tumor cell migration and invasion in gastric cancer cells.ConclusionOTUB1 contributes to gastric cancer development by enhancing tumor invasiveness. Targeting OTUB1 should be considered in future molecular therapies.
| S-EPMC4891435 | biostudies-literature
Project description:BackgroundGlioma is an aggressive tumor of the central nervous system. Caspase-6 (CASP6) plays a crucial role in cell pyroptosis and is a central protein involved in many cellular signaling pathways. However, the association between CASP6 and prognosis of glioma patients remains unclear.MethodsFour bioinformatic databases were analyzed to identify differentially expressed genes (DEGs) between glioma and healthy tissues. Eighty-one protein-coding pyroptosis-related genes (PRGs) were obtained from the GeneCards database. The pyroptosis-related DEGs (PRDEGs) were extracted from each dataset, and CASP6 was found to be aberrantly expressed in glioma. We then investigated the biological functions of CASP6 and the relationship between CASP6 expression and the tumor microenvironment and immunocyte infiltration. The half maximal inhibitory concentration of temozolomide and the response to immune checkpoint blockade in the high- and low-CASP6 expression groups were estimated using relevant bioinformatic algorithms. Quantitative real-time reverse transcription PCR and western blotting were carried out to confirm the different expression levels of CASP6 between human astrocytes and glioma cell lines (U251 and T98G). We determined the role of CASP6 in the tumorigenesis of glioma by knocking down CASP6 in U251 and T98G cell lines.ResultsWe found that CASP6 was overexpressed in glioma samples and in glioma cell lines. CASP6 expression in patients with glioma correlated negatively with overall survival. In addition, CASP6 expression correlated positively with the degree of glioma progression. Functional analysis indicated that CASP6 was primarily involved in the immune response and antigen processing and presentation. Patients with high CASP6 levels responded more favorably to temozolomide, while patients with low expression of CASP6 had a better response to immunotherapy. Finally, in vitro experiments showed that CASP6 knockdown inhibited glioma proliferation.ConclusionsThe pyroptosis-related gene CASP6 might represent a sensitive prognostic marker for patients with glioma and might predict their response of immunotherapy and temozolomide therapy. Our results might lead to more precise immunotherapeutic strategies for patients with glioma.
| S-EPMC9479196 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD), a malignancy with high incidence and mortality rates worldwide, contains multiple genomic and epigenomic abnormalities. And the useful tumor markers associated with these abnormalities need further investigation. Whereas apoptosis is a form of programmed cell death, the expression of apoptosis-related genes in LUAD and its relationship with prognosis is unclear. In the present study, we identified 64 differentially expressed apoptosis-related genes (DEARGs) that were differentially expressed between LUAD tissue and normal lung tissue. Based on these DEARGs, all LUAD cases were classified into two subtypes using The Cancer Genome Atlas (TCGA) cohort to assess the prognostic value of apoptosis-related genes for survival. An 11-gene signature was established by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method to construct a multigene prediction model and classify all LUAD patients in the TCGA cohort into high or low AS-score groups. Patients in the low AS-score group had significantly higher survival and prognosis than those in the high AS-score group. Taking the median risk score of the AS-score, LUAD patients in the GSE68465 cohort were divided into two risk groups, low and high. The overall survival (OS) time was longer in the low AS-score group. Combined with clinical characteristics, the AS-score was an independent predictor of LUAD patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses showed that the differential genes between the two groups were mainly enriched in cellular immunity. Further analysis revealed higher immune checkpoint protein expression and higher tumor mutational burden (TMB) in the high AS-score group, suggesting better efficacy of immunotherapy in the high AS-score group than the low AS-score group. And the high AS-score group was better in chemotherapy and targeted therapy efficiency. In conclusion, the AS-score constructed based on apoptosis-related genes can predict the prognosis of LUAD patients and provide some guidance for the antitumor treatment of LUAD patients.
| S-EPMC9094710 | biostudies-literature
Project description:BackgroundProtein-coding gene LIM Domain Kinase 1 (LIMK1) is upregulated in various tumors and reported to promote tumor invasion and metastasis. However, the prognostic values of LIMK1 and correlation with immune infiltrates in lung adenocarcinoma are still not understood. Therefore, we evaluated the prognostic role of LIMK1 and its correlation with immune infiltrates in lung adenocarcinoma.MethodsTranscriptional expression profiles of LIMK1 between lung adenocarcinoma tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). The LIMK1 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas. Receiver operating characteristic (ROC) curve was used to differentiate lung adenocarcinoma from adjacent normal tissues. Kaplan-Meier method was conducted to assess the effect of LIMK1 on survival. Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analyses were performed using the "ClusterProfiler" package. The relationship between LIMK1 mRNA expression and immune infiltrates was determined by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB).ResultsThe expression of LIMK1 in lung adenocarcinoma tissues was significantly upregulated than those in adjacent normal tissues. Increased LIMK1 mRNA expression was associated with lymph node metastases and high TNM stage. The ROC curve analysis showed that with a cutoff level of 4.908, the accuracy, sensitivity, and specificity for LIMK1 differentiate lung adenocarcinoma from adjacent controls were 69.5, 93.2, and 71.9%, respectively. Kaplan-Meier survival analysis showed lung adenocarcinoma patients with high- LIMK1 had a worse prognosis than those with low- LIMK1 (43.1 vs. 55.1 months, P = 0.028). Correlation analysis indicated LIMK1 mRNA expression was correlated with tumor purity and immune infiltrates.ConclusionUpregulated LIMK1 is significantly correlated with poor survival and immune infiltrates in lung adenocarcinoma. Our study suggests that LIMK1 can be used as a biomarker of poor prognosis and potential immune therapy target in lung adenocarcinoma.
| S-EPMC8209497 | biostudies-literature