Integrin-β6 Serves as a Potential Prognostic Serum Biomarker for Gastric Cancer
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ABSTRACT:
SUBMITTER: Li Z
PROVIDER: S-EPMC8593195 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionDespite enormous efforts during the past decades, pancreatic adenocarcinoma (PAC) remains one of the most deleterious cancer entities. A useful biomarker for early detection or prognosis of PAC does not yet exist. The goal of our study was the characterization of β6-integrin (ITGB6) as a novel serum tumor marker for refined diagnosis and prognosis of PAC. Serum ITGB6 levels were analyzed in 3 independent PAC cohorts consisting of retrospectively and prospectively collected serum and/or (metastatic) PAC tissue specimens.MethodsUsing 2 independent cohorts, we measured serum ITGB6 concentrations in 10 chronic pancreatitis patients, 10 controls, as well as in 27 (cohort 1) and 24 (cohort 2) patients with PAC, respectively. In these patients, we investigated whether ITGB6 serum levels correlate with known clinical and prognostic markers for PAC and whether they might differ between patients with PAC or benign inflammatory diseases of the pancreas.ResultsWe found that elevated serum ITGB6 levels (≥0.100 ng/mL) in patients suffering from metastasizing PAC presented an unfavorable prognostic outcome. By correlating the ITGB6 tissue expression in primary and metastatic PAC with clinical parameters, we found that positive ITGB6 expression in the tumor tissue is linked to increased serum ITGB6 levels in nonmetastatic PAC and correlates with carbohydrate antigen 19-9 and clinical outcome.DiscussionOur findings suggest that ITGB6 might serve as a novel serum biomarker for early diagnosis and prognosis of PAC. Given the limited specificity and sensitivity of currently used carbohydrate antigen 19-9-based assays, ITGB6 may have the potential to improve the diagnostic accuracy for PAC.
| S-EPMC8367066 | biostudies-literature
Project description:BackgroundUbiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect and biological functional mechanism of YOD1 in pancreatic cancer are still unclear.ResultsIn the GEO and TCGA databases, YOD1 mRNA expression is significantly up regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P < 0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8 + T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell, Immunohistochemistry (IHC), Western blot and Flow Cytometry indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells and affect the immune microenvironment.ConclusionOur results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.
| S-EPMC9158148 | biostudies-literature
Project description:Purpose:Circular RNAs (circRNAs) are novel type of noncoding RNAs that play important roles and serve as noninvasive biomarkers in various cancers. In the present study, we focused on circFoxO3a and aimed to investigate its prognostic value as a novel serum biomarker for squamous cervical cancer (SCC). Patients and Methods:Our study included 103 SCC patients from Obstetrics and Gynecology Hospital of Fudan University. Expression levels of circFoxO3a in the serum of patients with SCC were examined by reverse transcription?quantitative PCR (RT?qPCR). The correlation between serum circFoxO3a expression and clinicopathologic factors was analyzed. The Kaplan-Meier method and multivariate Cox regression analysis were applied to evaluate the independent prognostic factors for SCC. A prognostic predictive nomogram was constructed using R software. Results:Levels of serum circFoxO3a were decreased in SCC patients compared with controls. Low expression of circFoxO3a was correlated with deeper stromal invasion and positive lymph node metastasis. Moreover, SCC patients with lower expression of serum circFoxO3a showed poorer prognosis, including both overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox analysis indicated low serum circFoxO3a levels to be an unfavorable prognostic factor for both OS and RFS, independent of positive lymph node metastasis. Notably, the predictive nomogram we established further confirmed that serum circFoxO3a is a useful tool for predicting survival in SCC. Conclusion:Altogether, our findings demonstrated that serum circFoxO3a could serve as a potential novel noninvasive predictive prognostic biomarker and therapeutic target for SCC.
| S-EPMC7154007 | biostudies-literature
Project description:Neoadjuvant chemotherapy (NACT) has been established as being an effective treatment for advanced gastric cancer (GC), while the predictive biomarker of NACT efficacy remains under investigation. Aspartate β-hydroxylase (ASPH) represents an attractive target which is a highly conserved transmembrane enzyme overexpressed in human GC, and participates in the malignant transformation by promoting tumor cell motility. Here, we evaluated the expression of ASPH by immunohistochemistry in 350 GC tissues (including samples for NACT) and found that ASPH expression was higher in patients undergoing NACT compared with patients without NACT pre-operation. The OS and PFS time of ASPH-intensely positive patients was significantly shorter than that of the negative patients in the NACT group, while the difference was not significant in patients without NACT. We showed that ASPH knockout enhanced the inhibitory effects of chemotherapeutic drugs on the cell proliferation, migration, and invasion in vitro and suppressed tumor progression in vivo. Co-immunoprecipitation revealed that ASPH might interact with LAPTM4B to perform chemotherapeutic drug resistance. Our results suggested that ASPH might serve as a candidate biomarker to predict prognosis and a novel therapeutic target for gastric cancer patients treated with neoadjuvant chemotherapy.
| S-EPMC10053938 | biostudies-literature
Project description:PurposeCytochrome b561 (CYB561) is a transmembrane protein and participates in ascorbate recycling and iron homeostasis. However, its role in breast cancer remains unclear.Patients and methodsIn this study, we explored the expression pattern and prognostic value of CYB561 in breast cancer through The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), PrognoScan and Kaplan-Meier Plotter and confirmed its mRNA expression in human breast cell lines. LinkedOmics, Metascape and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were applied to investigate the co-expression genes and construct microRNA (miRNA) networks associated with CYB561. The correlations between CYB561 and immune infiltration cells and genes were also illustrated.ResultsThe CYB561 expression was upregulated in breast cancer tissues and cell lines and significantly correlated with the clinical features of breast cancer patients. High CYB561 expression was associated with poor survival and was an independent risk factor for overall and disease-specific survival. Functional enrichment analysis showed that CYB561 and its co-expressed genes were mainly enriched in lipid biosynthetic process, Wnt signaling pathway, Hippo signaling pathway, etc. The miRNA network analysis suggested that hsa-miR-497 was negatively correlated with CYB561 expression and was predicted to direct target CYB561. CYB561 expression was positively correlated with infiltrating levels of CD4+ T cells, neutrophils and dendritic cells in breast cancer. Subsequent analysis found that B cells could predict the outcome of breast cancer. Also, CYB561 showed strong correlations with diverse immune marker sets in breast cancer.ConclusionCYB561 may serve as a potential prognostic biomarker and target for breast cancer. Our findings laid foundation for future research on molecular mechanisms of CYB561 in breast cancer.
| S-EPMC8722309 | biostudies-literature
Project description:Glucosamine‑phosphate N‑acetyltransferase 1 (GNPNAT1) is a member of the acetyltransferase superfamily, related to general control non‑depressible 5 (GCN5). It has been documented that GNPNAT1 expression is increased in lung cancer, whereas its involvement in breast cancer (BC) remains to be further investigated. The present study aimed to evaluate the expression levels of GNPNAT1 in BC and its effect on BC stem cells (BCSCs). The Cancer Genome Atlas (TCGA) database was used for the analysis of the expression of GNPNAT1 and its clinical significance. Cox regression and logistic regression analyses were used to evaluate prognosis‑related factors. The GNPNAT1‑binding protein network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) application. The biological signaling pathways implicated in GNPNAT1 were investigated through function enrichment analysis including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. The single‑sample GSEA method was used to investigate the connection between the level of immune infiltration and GNPNAT1 expression in BC. GNPNAT1 expression was upregulated in patients with BC and was significantly associated with a poor prognosis. GNPNAT1 and its co‑expressed genes were mostly enriched in nuclear transport, Golgi vesicle transport, ubiquitin‑like protein transferase activity and ribonucleoprotein complex binding, as determined using functional enrichment analysis. GNPNAT1 expression was positively associated with Th2 cells and T‑helper cells, and negatively associated with plasmacytoid dendritic cells, CD8+ T‑cells and cytotoxic cells. Additionally, the GNPNAT1 expression levels were considerably increased in BCSCs. GNPNAT1 knockdown markedly decreased the stemness ability of SKBR3 and Hs578T cells, including the production of CSC markers and mammosphere or clone formation, while GNPNAT1 overexpression increased the stemness level. Hence, the findings of the present study demonstrate that GNPNAT1 may be exploited as a novel prognostic biomarker and therapeutic target for BC.
| S-EPMC10326828 | biostudies-literature
Project description:BackgroundThe tumor microenvironment (TME) plays an important role in the growth and expansion of gastric cancer (GC). Studies have identified that CD93 is involved in abnormal tumor angiogenesis, which may be related to the regulation of the TME.AimTo determine the role of CD93 in GC.MethodsTranscriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas. Additionally, RNA-seq data sets from Gene Expression Omnibus (GSE118916, GSE52138, GSE79973, GSE19826, and GSE84433) were applied to validate the results. We performed the immune infiltration analyses using ESTIMATE, CIBERSORT, and ssGSEA. Furthermore, weighted gene co-expression network analysis (WGCNA) was conducted to identify the immune-related genes.ResultsCompared to normal tissues, CD93 significantly enriched in tumor tissues (t = 4.669, 95%CI: 0.342-0.863, P < 0.001). Higher expression of CD93 was significantly associated with shorter overall survival (hazard ratio = 1.62, 95%CI: 1.09-2.4, P = 0.017), less proportion of CD8 T and activated natural killer cells in the TME (P < 0.05), and lower tumor mutation burden (t = 4.131, 95%CI: 0.721-0.256, P < 0.001). Genes co-expressed with CD93 were mainly enriched in angiogenesis. Moreover, 11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.ConclusionCD93 is a novel prognostic and diagnostic biomarker for GC, that is closely related to the immune infiltration in the TME. Although this retrospective study was a comprehensive analysis, the prospective cohort studies are preferred to further confirm these conclusions.
| S-EPMC9928705 | biostudies-literature
Project description:Colorectal cancer (CRC) is the second leading cause of cancer-associated mortality worldwide. Currently, available diagnostic biomarkers are neither sensitive nor specific. Thus, the present study aimed to identify novel circulating microRNAs (miRNAs) as biomarkers for the early diagnosis of CRC. All samples were provided by The Second Affiliated Hospital of Nanjing Medical University (Nanjing, China). Analysis of the GSE108153 and GSE55139 datasets, downloaded from the Gene Expression Omnibus (GEO) database was performed using the online tool, GEO2R. Reverse transcription-quantitative PCR was performed to determine miR-592 expression in CRC tissues, cells and serums of patients. Subsequently, the diagnostic value of serum miR-592 was assessed via receiver operating characteristic (ROC) curve analysis. Both the assessment of clinical samples and bioinformatics analysis demonstrated that miR-592 expression levels were significantly upregulated in the tissues and serum of patients with CRC, suggesting that elevated serum miR-592 may be tumor-derived. ROC analysis indicated that serum miR-592 levels may differentiate patients with early stage CRC and advanced adenoma from healthy individuals, with area under the curve values of 0.801 and 0.747, respectively. Taken together, the results of the present study suggest that serum miR-592 may be implicated as a potential biomarker for the early diagnosis of CRC.
| S-EPMC7377022 | biostudies-literature
Project description:Serine-rich splicing factor3 (SRSF3) plays an essential role in cell proliferation and inducing and maintaining of cancers as a proto-oncogene. However, the mechanisms of SRSF3 in pan-cancers are still unknown. In our study, a visualized prognostic landscape of SRSF3 in pan-cancer was investigated and the relationship between SRSF3 expression and immune infiltration was also investigated. The expression pattern and prognostic worth of SRSF3 among pan-cancers were explored through different databases, namely, the TCGA and Kaplan-Meier Plotter. Moreover, the survival analysis including Kaplan-Meier method for evaluating between groups was conducted. Further analyses including the correlation between expression SRSF expression and immune infiltration including tumor mutation burden (TMB), microsatellite instability (MSI) was investigated using Spearman test. In ACC, KIRP and UCEC cancer, upregulated expression of SRSF3 was associated with worse disease-free interval (DFI), representing a mechanism in promoting progression of tumor. Our results showed that SRSF3 expression was positively correlated immune cell infiltration, TMB, MSI in certain cancer types, indicating SRSF3 expression to potential value of therapy response. Additionally, we explored the functional characteristics of SRSF in vitro through western blot detecting the expression level of the apoptosis-related proteins in SW480 and 786-O cells. SRSF3 expression was upregulated in pan-cancer tissue compared with normal tissue, which confirmed by immunohistochemistry and its expression indicated poor overall survival and death-specific survival. Therefore, SRSF3 was found to be a possible biomarker for prognostic and therapeutic assessment through bioinformatic analysis. SRSF3 is expressed in various cancers and its high expression correlated to poor survival and disease progression. In summary, SRSF3 expression can be considered as a prognostic biomarker in pan-cancer and therapeutic evaluation.
| S-EPMC9047863 | biostudies-literature
Project description:Cholangiocarcinoma is a devastating malignancy that is notoriously difficult to diagnose and is associated with a high mortality. Despite extensive efforts to improve the diagnosis and treatment of this neoplasm, limited progress has been made. Integrin β6 is a subtype of integrin that is expressed exclusively on the surfaces of epithelial cells and is associated with a variety of tumors. In the present study, we investigated the expression and roles of integrin β6 in cholangiocarcinoma. β6 upregulation in cholangiocarcinoma was correlated with lymph node metastasis and distant metastasis. Moreover, integrin β6 was identified as a biomarker for the diagnosis of cholangiocarcinoma and an indicator of lymph node metastasis. Integrin β6 significantly promoted the proliferation, migration and invasion of cholangiocarcinoma cells. Furthermore, integrin β6 increased Rac1-GTPase, resulting in the upregulation of metalloproteinase-9 (MMP9) and F-actin polymerization. Taken together, our results indicate that integrin β6 promotes tumor invasiveness in a Rac1-dependent manner and is a potential biomarker for tumor metastasis. Integrin β6 may help to improve the diagnostic accuracy, and targeting β6 may be a novel strategy for the treatment of cholangiocarcinoma.
| S-EPMC4954992 | biostudies-literature