Expression mode and prognostic value of FXYD family members in colon cancer.
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ABSTRACT:
SUBMITTER: Jin M
PROVIDER: S-EPMC8351680 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Colon adenocarcinoma (COAD) is among the most prevalent cancers worldwide, ranking as the third most prevalent malignancy in incidence and mortality. The somatostatin receptor (SSTR) family comprises G-protein-coupled receptors (GPCRs), which couple to inhibitory G proteins (Gi and Go) upon binding to somatostatin (SST) analogs. GPCRs are involved in hormone release, neurotransmission, cell growth inhibition, and cancer suppression. However, their roles in COAD remain unclear. This study used bioinformatics to investigate the expression, prognosis, gene alterations, functional enrichment, and immunoregulatory effects of the SSTR family members in COAD. SSTR1-4 are differentially downregulated in COAD, and low SSTR2 expression indicates poor survival. Biological processes and gene expression enrichment of the SSTR family in COAD were further analyzed using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology. A strong correlation was observed between SSTR expression and immune cell infiltration. We also quantified SSTR2 expression in 25 COAD samples and adjacent normal tissues using quantitative real-time polymerase chain reaction. We analyzed its correlation with the dendritic cell-integrin subunit alpha X marker gene. The biomarker exploration of the solid tumors portal was used to confirm the correlation between SSTR2 with immunomodulators and immunotherapy responses. Our results identify SSTR2 as a promising target for COAD immunotherapy. Our findings provide new insights into the biological functions of the SSTR family and their implications for the prognosis of COAD.
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Project description:BACKGROUND Colorectal cancer (CRC), the most common gastrointestinal cancer, is associated with high mortality rates. Enolase is a major enzyme present in the glycolytic pathway. However, the functional significance of the enolase (ENO) gene family in the pathogenesis of CRC has been unclear. MATERIAL AND METHODS The data associated with 438 CRC patients from The Cancer Genome Atlas database were extracted for analysis. Survival analyses with Cox regression was performed to construct a prognostic signature. We investigated the processes that underlies the correlation between ENO genes and overall survival (OS) using gene set enrichment analysis (GSEA). We then developed a connectivity map to identify candidate target drugs for CRC. RESULTS The multivariate survival analysis showed that low expression of ENO2 and ENO3 had a significant correlation with longer OS. The joint-effects survival analysis indicated that the combined low expression of ENO2 and ENO3 was highly correlated with favorable OS. As indicated by the gene set enrichment analysis (GSEA), the ENO gene is involved in various biological pathways and has multiple roles. Potential pharmacological targets of ENO2 and ENO3 were constructed as well. CONCLUSIONS Low expression levels of both ENO2 and ENO3 were linked to a positive prognosis for CRC. Both ENO2 and ENO3 show promise as prognostic biomarkers for colon cancer patients.
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Project description:Background:Increased aberrant expression or activation of the epidermal growth factor receptor (EGFR) family members has been reported in a wide range of cancers, and the EGFR family of tyrosine kinases has emerged as an important therapeutic target in malignancies. However, the expression patterns and exact roles of each distinct EGFR family member, which contribute to tumorigenesis and progression of ovarian cancer (OC), are yet to be elucidated. Materials and methods:In the current study, we report the distinct expression and prognostic value of EGFR family members in patients with OC by analyzing a series of databases including ONCOMINE, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, and Database for Annotation, Visualization and Integrated Discovery . Results:It was found that in patients with OC, mRNA expression levels of ERBB2/3/4 were significantly upregulated, whereas the transcription levels of EGFR were downregulated. Aberrant EGFR expression and ERBB2/3/4 mRNA levels were associated with OC prognosis. Conclusion:These results suggest that EGFR and ERBB3/4 are distinct prognostic biomarkers and may be potential targets for OC. These results may be beneficial to better understand the molecular underpinning of OC and may be useful to develop tools for more accurate OC prognosis and for promoting the development of EGFR-targeted inhibitors for OC treatment.
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Project description:The aim of the present study was to investigate the potential prognostic value of members of the heat shock protein (HSP)90 family in non-small cell lung cancer (NSCLC) patients. The mRNA expression profiles of 1,926 NSCLC patients, which was available from the Kaplan-Meier plotter database, were included in the study. High expression of HSP90AA1 mRNA was significantly associated with a poorer rate of overall survival (OS) for all NSCLC patients [hazard ratio (HR), 1.21; 95% confidence interval (CI): 1.06-1.37; P=0.004], as well as for patients with adenocarcinoma (ADE; HR, 1.3; 95% CI: 1.02-1.65; P=0.034), but no significant correlation was identified for squamous cell carcinoma (SCC) patients (HR, 1.08; 95% CI: 0.85-1.38; P=0.51). High expression of HSP90AB1 and HSP90B1 mRNA was significantly associated with poorer rates of OS in lung SCC and ADE patients combined, as well as in lung ADE patients alone. By contrast, high expression of tumor necrosis factor receptor-associated protein 1 (TRAP1) mRNA was significantly associated with improved OS rates in all NSCLC patients combined (HR, 0.88; 95% CI: 0.77-0.99; P=0.041), as well as ADE patients. In stratified survival analysis, a high expression of HSP90AA1, HSP90AB1 and HSP90B1 predicted poor prognosis in stage I NSLCC patients, suggesting that these genes may serve as stage-independent prognostic indicators. As an elevated expression of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 was associated with poorer OS outcomes in patients with NSCLC, these HSP90 members may be potential prognostic biomarkers and drug targets for the treatment of NSCLC.
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Project description:Objective: Colorectal cancer (CRC) is one of the common malignant tumors worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and are implicated in the development of multiple cancers by blocking differentiation and promoting proliferation. However, little is known about the function of distinct CBX proteins in colorectal cancer. Methods: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of CBXs in colorectal cancer patients. Results: The expression levels of CBX1/2/3/4/5 and CBX8 were significantly elevated in CRC tissues, whereas the expression levels of CBX6/7 were reduced. CBX3 was significantly associated with the clinical cancer stage and short disease-free survival (DFS) in CRC patients. High mRNA expression of CBX5/6 was associated with short overall survival (OS) in rectal cancer patients. CBX3/5/6 could be potential prognostic biomarkers for the survival of CRC patients. Moreover, the functions of the differentially expressed CBXs were primarily related to the SUMOylation of DNA methylation proteins and chromatin organization and may regulate the pluripotency of stem cells. The expression of CBXs were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells in colon cancers and rectal cancers. Conclusions: Our study may provide novel insights for the selection of prognostic biomarkers of CBX family in colorectal cancer.
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Project description:Managing low-grade gliomas (LGG) remains a major medical challenge due to the infiltrating nature of the tumor and failure of surgical resection to eliminate the disease. EMILIN/Multimerins contain the gC1q signature, which is involved in many tumor processes. However, the expression and prognostic value of EMILIN/Multimerins in LGG remains unclear. This study used integrated bioinformatics analysis to investigate the expression pattern, prognostic value and function of EMILIN/Multimerins in patients with LGG. We analyzed the transcription levels and prognostic value EMILIN/Multimerins in LGG using the ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN databases. The mutation and co-expression rates of neighboring genes in EMILIN/Multimerins were studied using cBioPortal. TIMER and Metascape were used to reveal the potential function of EMILIN/Multimerins in LGG. According to our analysis, most EMILIN/Multimerins were overexpressed in LGG and shared a clear association with immune cells. GEPIA analysis confirmed that high levels of EMILIN/Multimerins, not including MMRN2, were associated with a poor prognosis in disease-free survival of patients with LGG. Additionally, we discovered that EMILIN/Multimerins may regulate LGG and we found a correlation between their expression patterns and distinct pathological grades. We found that EMILIN/Multimerins serve as possible prognostic biomarkers and high-priority therapeutic targets patients with LGG.
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Project description:Liver cancer is the fifth most prevalent malignant tumor, while hepatocellular carcinoma represents the most prevalent subtype worldwide. Previous studies have associated the chromobox family, critical components of epigenetic regulatory complexes, with development of many malignancies owing to their role in inhibiting differentiation and promoting proliferation of cancer cells. However, little is known regarding their function in development and progression of hepatocellular carcinoma. In the present study, we analyzed differential expression, prognostic value, immune cell infiltration, and gene pathway enrichment of chromobox family in hepatocellular carcinoma patients. Next, we performed Pearson's correlation analysis to determine the relationships between chromobox family proteins with tumor-immune infiltration. Results revealed that high expression of CBX1, CBX2, CBX3, CBX6, and CBX8 was associated with poor survival rates of hepatocellular carcinoma patients. These five factors were used to build prognostic gene models using LASSO Cox regression analysis. Results indicated that high expression of CBX2 and CBX3 proteins was significantly associated with poor prognosis for hepatocellular carcinoma patients. The resulting nomogram revealed that CBX3 and T stages were significantly correlated with prognosis of hepatocellular carcinoma patients. Notably, predictive CBX3 was strongly correlated with immune cell infiltration. Furthermore, results from functional enrichment analysis revealed that CBX3 was mainly involved in regulation of methylation of Histone H3-K27. Collectively, these findings suggest that CBX3 could be a biomarker for predicting prognosis of hepatocellular carcinoma patients.
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Project description:C-X-C motif chemokine ligand 17 (CXCL17) is a mucous chemokine and its expression is highly correlated with that of G protein-coupled receptor 35 (GPR35), which has been confirmed as its receptor and named C-X-C motif chemokine receptor 8 (CXCR8). CXCL17 is upregulated in several types of cancer. However, the biological role of this chemokine in colon cancer remains unknown. In the present study, the expression levels of CXCL17 and CXCR8 were examined using immunohistochemistry in 101 colon cancer tissues and 79 healthy tumour-adjacent tissues. CXCL17 and CXCR8 expression levels were increased in the colon cancer samples compared with tumour-adjacent samples. Patients with high CXCL17 expression had longer overall survival (OS) compared with patients with low expression of CXCL17 (log-rank test; P=0.027). However, CXCR8 expression, but not CXCL17, was an independent prognostic factor for OS in patients with colon cancer. The expression of CXCR8 correlated positively with that of CXCL17 in colon cancer samples (?=0.295; P=0.003). Furthermore, the combined high expression of CXCL17 and CXCR8 was a significant independent prognostic factor for OS in patients with colon cancer (P=0.001). In subgroups with a TNM stage of I-II, the patients with combined high expression of CXCL17 and CXCR8 had a longer survival compared with those without combined high expression (P=0.001). However, this difference was not observed in subgroups with a TNM stage of III-IV. Collectively, these findings suggest that CXCL17/CXCR8 signalling may be involved in colon cancer and contribute to improved patient outcomes.
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Project description:Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.
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Project description:BackgroundEsophageal cancer (EC) is one of the most common human malignant tumors worldwide. Chromobox (CBX) family proteins are significant components of epigenetic regulatory complexes. It is reported that CBXs play critical roles in the oncogenesis and development of various tumors. Nonetheless, their functions and specific roles in EC remain vague and obscure.Methods and materialsWe used multiple bioinformatics tools, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), UALCAN, Kaplan-Meier plotter, cBioPortal, Metascape, TIMER2 and TISIDB, to investigate the expression profile, gene alterations and prognostic roles of CBX family proteins, as well as their association with clinicopathologic parameters, immune cells and immune regulators. In addition, RT-qPCR, Western blot, CCK8, colony formation, wound healing and transwell assays were performed to investigate the biological functions of CBX3 in EC cells.ResultsCBX3 and CBX5 were overexpressed in EC compared to normal tissues. Survival analysis revealed that high expression of CBX1 predicted worse disease-free survival (DFS) in EC patients. Functionally, CBXs might participate in mismatch repair, spliceosome, cell cycle, the Fanconi anemia pathway, tight junction, the mRNA surveillance pathway and the Hippo signaling pathway in EC development. Furthermore, CBXs were related to distinct immune cells infiltration and immune regulators. Additionally, depletion of CBX3 inhibited the proliferation, migration and invasion abilities of EC cells.ConclusionsOur study comprehensively investigated the expression pattern, prognostic value, and gene alterations of CBXs in EC, as well as their relationships with clinicopathologic variables, immune cells infiltration and immune regulators. These results suggested that CBX family proteins, especially CBX3, might be potential biomarkers in the progression of EC.
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