Reduced tissue and serum resistin expression as a clinical marker for esophageal squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Hung AC
PROVIDER: S-EPMC8442229 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study was aimed to assess serum microRNA-30d-5p (miR-30d-5p) expression in patients with esophageal squamous cell carcinoma before and after operation, exploring its associations with clinical pathological parameters. A total of 30 esophageal cancer patients who underwent radical resection and were pathologically confirmed with esophageal squamous cell carcinoma in the First Affiliated Hospital of Anhui Medical University, from April to May in 2013, were enrolled, alongside 19 healthy controls. The expression levels of miRNA in serum from patients with esophageal squamous cell carcinoma before and after operation were assessed by microarrays and real-time PCR (RT-PCR). The associations of miR-30d-5p expression with clinical pathological parameters were determined. Serum hsa-miR-30d-5p levels in patients with esophageal squamous cell carcinoma (study group) were significantly associated with the tumor depth of invasion, lymph node metastasis, tumor location and length, histopathological type and degree of differentiation, as well as history of smoking and drinking (P<0.05). Moreover, changes of serum miRNA levels were more prominent than that of thymidine kinase 1 (TK1). There were significant differences in hsa-miR-30d-5p expression levels between the study and control groups (P<0.05). These results indicated that microRNA-30d-5p is a potential marker of esophageal squamous cell carcinoma, with high expression having a certain promoting role in the occurrence and development of esophageal cancer.
| S-EPMC6965463 | biostudies-literature
Project description:ObjectiveMiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells.DesignMiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion.ResultsMiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4.ConclusionsMiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in "activating" fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment.
| S-EPMC3769386 | biostudies-literature
Project description:MicroRNAs (miRNAs) and inflammatory genes have a role in the initiation and development of esophageal squamous cell carcinoma (ESCC). In our study, we examined the potential of using miRNA and inflammatory gene expression patterns as prognostic classifiers for ESCC. Five miRNAs and 25 inflammatory-related genes were measured by quantitative reverse transcriptase PCR in tumor tissues and adjacent noncancerous tissues from 178 Chinese patients with ESCC. The expression levels of miR-21 (p = 0.027), miR-181b (p = 0.002) and miR-146b (p = 0.021) in tumor tissue and miR-21 (p = 0.003) in noncancerous tissue were associated with overall survival of patients. These data were combined to generate a miRNA risk score that was significantly associated with worse prognosis (p = 0.0001), suggesting that these miRNAs may be useful prognostic classifiers for ESCC. To construct an inflammatory gene prognostic classifier, we divided the population into training (n = 124) and test cohorts (n = 54). The expression levels of CRY61, CTGF and IL-18 in tumor tissue and VEGF in adjacent noncancerous tissue were modestly associated with prognosis in the training cohort |Z-score| > 1.5 and were subsequently used to construct a Cox regression-based inflammatory risk score (IRS). IRS was significantly associated with survival in both the training cohort (p = 0.002) and the test cohort (p = 0.005). Furthermore, Cox regression models combining both miRNA risk score and IRS performed significantly better than models with either alone (p < 0.001 likelihood ratio test). Therefore, miRNA and inflammatory gene expression patterns, alone or in combination, have potential as prognostic classifiers for ESCC and may help to guide therapeutic decisions.
| S-EPMC6503976 | biostudies-literature
Project description:BackgroundEpidermal growth factor receptor (EGFR), c-Met, and human epidermal growth factor receptor 2 (HER2) are overexpressed in a variety of human cancers, and may serve as biomarkers for disease prognosis. We examined whether high expression of these molecular markers correlates with poor disease prognosis in esophageal squamous cell cancer (ESCC).Materials and methodsExpression of EGFR, c-Met, and HER2 protein was detected by immunohistochemistry (IHC) in 180 paraffin-embedded tissue samples from stage IIB-IIIC ESCC patients. The overall survival (OS) rates were calculated according to the Kaplan-Meier method, and the log-rank test was used to evaluate differences between survival curves. The Cox proportional hazards model was used for univariate and multivariate analyses.ResultsThe median survival of all patients was 46 months. There was no significant difference in OS in terms of HER2 and EGFR status (P = 0.177 and P=0.061, respectively). However, there was a significant difference in OS between c-Met high expression patients and c-Met low expression or negative patients (median: 41.9 months vs. 56.7 months; P = 0.001). Multivariate analysis also showed that, of the covariates analyzed, c-Met high expression was the only prognostic factor for OS (HR: 0.459 [95 % confidence interval: 0.287-0.733]; P = 0.001). Patients with ESCC that had concurrent overexpression of EGFR and c-Met had significantly worse survival than ESCC that displayed overexpression of either EGFR or c-Met individually or that did not have overexpression of either protein (P=0.000).ConclusionsOverexpression of HER2 and EGFR individually is not significantly associated with poor prognosis in ESCC. High expression of c-Met may be indicative of a poorer prognosis in ESCC. In order to promote efficient and rapid development of therapeutic methods in ESCC, further studies are necessary to explore the role of c-Met.
| S-EPMC4820735 | biostudies-literature
Project description:BACKGROUND:c-Met, one of current potential hot targets, has been suggested as a potential tumor marker in the development of esophageal squamous cell carcinoma (ESCC). Our aim was to investigate the expression of c-Met in advanced esophageal squamous cell carcinoma in four phase II trials who had tumor tissues from archival in our center and analyze the correlations between c-Met expression and clinical features. METHODS:Ninety patients with advanced ESCC who were admitted to the phase II clinical trials in the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute from March 2007 to March 2014 were finally eligible for present study and the corresponding tissues and clinical data were collected. The expression of c-Met in the tissue samples was detected by immunohistochemistry (IHC). c-Met overexpression was defined as???the median value of H-score. Kaplan-Meier and Cox multivariate regression were conducted to evaluate the relationship between c-Met expression and ESCC survival. RESULTS:The overexpression of c-Met is 43.3% in advanced ESCC. There was no statistical difference between c-Met expression and clinical features except sex and tumor location. Survival analysis documented that the overexpression of c-Met predicted a worse prognosis (OS: 253 d vs 422 d, P?=?0.011). In the group treated with chemotherapy combined with anti-EGFR drugs, patients with lowexpression of c-Met had a better OS than those with overexpression of c-Met (OS: 577 d vs 232 d, P?=?0.007). CONCLUSIONS:c-Met may be an independent prognostic factor in advanced ESCC. The overexpression of c-Met may predict a worse efficacy of anti-EGFR therapy.
| S-EPMC4307685 | biostudies-literature
Project description:Tripartite motif-containing 24 (TRIM24), a member of the transcription intermediary factor 1 family, is defined as a co-regulator with several nuclear receptors, such as RAR?. TRIM24 has been reported to be involved in many cancers. In this study, we aimed to investigate the expression pattern and prognostic significance of TRIM24 and its relationship with RAR? in esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR and western blot. Immunohistochemistry staining shows that the reduced TRIM24 protein is associated with lymph node metastasis (P=0.024), advance pathological TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated TRIM24 protein predicts longer overall survival and disease-free survival (both P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI, 0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve prediction of survival of pTNM stage in ESCC patients, especially in stage I and II. However, no significant relationship was found between TRIM24 and RAR? expression levels. In conclusion, reduced TRIM24 protein is associated with poor survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC.
| S-EPMC5076458 | biostudies-literature
Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers.MethodsClinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC.ResultsA total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc.ConclusionSeveral collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.
| S-EPMC6779144 | biostudies-literature
Project description:Sample labeling and array hybridization were performed according to the Agilent One-Color Microarray-Based Gene Expression Analysis protocol (Agilent Technology) with minor modifications. Briefly, mRNA was purified from total RNA after removal of rRNA (mRNA-ONLY™ Eukaryotic mRNA Isolation Kit, Epicentre). Then, each sample was amplified and transcribed into fluorescent cRNA along the entire length of the transcripts without 3' bias utilizing a random priming method (Arraystar Flash RNA Labeling Kit, Arraystar). The labeled cRNAs were purified by RNeasy Mini Kit (Qiagen). The concentration and specific activity of the labeled cRNAs (pmol Cy3/μg cRNA) were measured by NanoDrop ND-1000. 1 μg of each labeled cRNA was fragmented by adding 5 μl 10 × Blocking Agent and 1 μl of 25 × Fragmentation Buffer, then heated the mixture at 60°C for 30 min, finally 25 μl 2 × GE Hybridization buffer was added to dilute the labeled cRNA. 50 μl of hybridization solution was dispensed into the gasket slide and assembled to the LncRNA expression microarray slide. The slides were incubated for 17 hours at 65°C in an Agilent Hybridization Oven. The hybridized arrays were washed, fixed and scanned with using the Agilent DNA Microarray Scanner (part number G2505C).
2021-12-30 | GSE192662 | GEO
Project description:The aim was to analyze the association between exosomal microRNA (miR)-766-3p expression levels in serum and the prognosis of esophageal squamous cell carcinoma (ESCC). The serum global exosomal miRNA expression of ESCC patients was measured by microRNA microarray. Quantitative real-time PCR was used to analyze the expression levels of candidate miRNAs in both serum and tissues from ESCC patients. Wilcoxon tests were applied to evaluate clinical characteristics and their association with serum levels of exosomal miR-766-3p. A Cox regression model was used to identify prognostic factors. The effects of miR-766-3p expression on cell migration and invasion were examined using Transwell assays, and CCK-8 assays were carried out to measure cell proliferation. The TNM stage was associated with high serum exosomal miR-766-3p levels of ESCC patients (P = .030). Higher serum exosomal miR-766-3p expression levels were associated with poor prognosis (for overall survival, hazard ratio [HR] [95% confidence interval (CI)], 2.21 [1.00, 4.87]; for disease-free survival, HR [95% CI], 2.15 [1.01, 4.59]). However, we found no association between the expression of miR-766-3p in tissue and ESCC prognosis. In vitro results showed that miR-766-3p promotes cell migration and invasion, but not cell proliferation. By using dual-luciferase reporter assay, HOXA13 was confirmed as a direct target gene of miR-766-3p. The ESCC patients with highly expressed serum exosomal miR-766-3p had a significantly worse survival. Therefore, serum exosomal miR-766-3p could serve as a prognostic marker for the assessment of ESCC.
| S-EPMC7540979 | biostudies-literature
Project description:BACKGROUND: Previous metabolomics studies have found differences in metabolic characteristics between the healthy and ESCC patients. However, few of these studies concerned the whole process of the progression of ESCC. This study aims to explore serum metabolites associated with the progression of ESCC. METHODS: Serum samples from 653 participants (305 normal, 77 esophagitis, 228 LGD, and 43 HGD/ESCC) were examined by ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). Principal component analysis (PCA) was first applied to obtain an overview of the clustering trend for the multidimensional data. Fuzzy c-means (FCM) clustering was then used to screen metabolites with a changing tendency in the progression of ESCC. Univariate ordinal logistic regression analysis and multiple ordinal logistic regression analysis were applied to evaluate the association of metabolites with the risk of ESCC progression, and adjusted for age, gender, BMI, tobacco smoking, and alcohol drinking status. RESULTS: After FCM clustering analysis, a total of 38 metabolites exhibiting changing tendency among normal, esophagitis, LGD, and HGD/ESCC patients. Final results showed 15 metabolites associated with the progression of ESCC. Ten metabolites (dopamine, L-histidine, 5-hydroxyindoleacetate, L-tryptophan, 2'-O-methylcytidine, PC (14:0/0:0), PC (O-16:1/0:0), PE (18:0/0:0), PC (16:1/0:0), PC (18:2/0:0)) were associated with decreased risk of developing ESCC. Five metabolites (hypoxanthine, inosine, carnitine (14:1), glycochenodeoxycholate, PC (P-18:0/18:3)) were associated with increased risk of developing ESCC. CONCLUSIONS: These results demonstrated that serum metabolites are associated with the progression of ESCC. These metabolites are capable of potential biomarkers for the risk prediction and early detection of ESCC.
| S-EPMC8100812 | biostudies-literature