Prognostic significance of TCF21 mRNA expression in patients with lung adenocarcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Xiao J
PROVIDER: S-EPMC5435710 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
Prognostic significance of TCF21 mRNA expression in patients with lung adenocarcinoma.
Xiao Jian J Liu Aibin A Lu Xiaoxiao X Chen Xi X Li Wei W He Shuya S He Bixiu B Chen Qiong Q
Scientific reports 20170517 1
Several prognostic indicators have shown inconsistencies in patients of different genders with lung adenocarcinoma, indicating that these variations may be due to the different genetic background of males and females with lung adenocarcinoma. In this study, we first used the Gene-Cloud of Biotechnology Information (GCBI) bioinformatics platform to identify differentially expressed genes (DEGs) that eliminated gender differences between lung adenocarcinoma and normal lung tissues. Then, we screen ...[more]
Similar Datasets
Project description:BACKGROUND:Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis. METHODS:IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the effect of IMMT expression on survival. RESULTS:High-IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06-3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation. CONCLUSION:Here, we first demonstrated that high-IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.
| S-EPMC6825906 | biostudies-other
Project description:Background and objectivesIn a previous genome-wide screening, we identified hypermethylated CpG islands around glutamate decarboxylase 1 (GAD1) in lung adenocarcinoma (LADC). In this study, we aimed to investigate the methylation and expression status of GAD1 and its prognostic value in patients with LADC.MethodsGAD1 methylation and mRNA expression status were analyzed using 33 tumorous and paired non-tumorous LADC samples and publicly available datasets. The prognostic value of GAD1 overexpression was investigated using publicly available datasets of mRNA levels and 162 cases of LADC by immunohistochemistry.ResultsThe methylation and mRNA expression levels of GAD1, each having a positive correlation, were significantly higher in LADC tumors than in paired non-tumorous tissues. LADC patients with higher GAD1 mRNA expression showed significantly poorer prognosis for overall survival in publicly available datasets. Higher immunoreactivity of GAD1 was significantly associated with the pathological stage, pleural invasion, lymph vessel invasion, and poorer prognosis for cancer-specific and disease-free survival. Multivariate analysis revealed that GAD1 protein overexpression is an independent prognosticator for disease-free survival.ConclusionsGAD1 mRNA and protein expression levels were significant prognostic factors in LADC, suggesting that they might be useful biomarkers to stratify patients with worse clinical outcomes after resection.
| S-EPMC6675743 | biostudies-literature
Project description:BackgroundRecent studies have demonstrated that upregulation of heat shock transcription factor 2 binding protein (HSF2BP) may promote genomic instability, thereby leading to the development of tumors and also providing a potential target for biological antitumor therapy. However, the role of HSF2BP has so far remained unclear in lung adenocarcinoma (LUAD).MethodsTo explore the function of HSF2BP in LUAD, we collected transcriptome data for 551 lung samples from The Cancer Genome Atlas (TCGA) database and methylation data for 461 lung samples from the University of California Santa Cruz (UCSC) genome database, in addition to corresponding clinical information. We used bioinformatic approaches to systematically explore the role of HSF2BP in LUAD, including Gene Set Enrichment Analysis (GSEA), coexpression analysis, the Tumor IMmune Estimation Resource (TIMER) tool, Connectivity Map (CMap) analysis, and a meta-analysis involving three Gene Expression Omnibus (GEO) datasets and one TCGA dataset.ResultsOur results found that upregulation of HSF2BP in LUAD was an independent risk factor for the prognosis and diagnosis of LUAD. GSEA analysis showed HSF2BP expression was associated with vital signaling pathways, including the cell cycle, P53 signaling pathway, and homologous recombination. Coexpression analysis revealed 10 HSF2BP-associated genes, including oncogenes and tumor suppressor genes. Additionally, we found that HSF2BP expression was negatively correlated with B-cell infiltration and had a potential interaction with CD80 in LUAD, which may play an important role in tumor immune escape. Finally, we identified four small-molecule drugs which show promise for LUAD treatment.ConclusionsThe present study found that elevated HSF2BP posed a threat to prognosis in LUAD patients. HSF2BP might have been involved in tumorigenesis by influencing genomic stability and contributing to tumor immune evasion in the tumor immune microenvironment of LUAD. These findings suggest that HSF2BP may provide a vulnerable target for improving and enhancing treatment of LUAD.
| S-EPMC8576644 | biostudies-literature
Project description:Chemokines are a family of small cytokines, which are signalling proteins secreted by cells. The principal role of chemokines is to serve as chemoattractants to guide the migration of their target cells. Chemokine C-X3-C motif ligand 1 (CX3CL1) is a protein-coding gene of fractalkine, which serves as a ligand for chemokine C-X3-C motif receptor 1 (CX3CR1) and integrins. However, the roles of CX3CL1 in different pathological types of lung cancer remain poorly understood. The present study aimed to investigate the potential clinical and biological function of CX3CL1 mRNA expression in patients with lung cancer. In the present study, lung cancer data obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas were downloaded and analysed, and the results demonstrated that an increased CX3CL1 mRNA expression in tumour tissues from lung adenocarcinoma (LUAD) was associated with improved overall survival. However, no significant association was identified between CX3CL1 expression and the prognosis of lung squamous cell carcinoma (LUSC). Furthermore, the genes whose expression levels were correlated with CX3CL1 expression were subjected to enrichment analysis, and the results for the LUAD data demonstrated that the most significant biological processes included 'positive regulation of cell adhesion', 'leukocyte cell-cell adhesion', 'leukocyte migration' and 'T cell activation', whereas, the important highly ranked pathways included 'cell adhesion molecules (CAMs)', 'leukocyte transendothelial migration' and 'natural killer cell-mediated cytotoxicity'. However, in the patients with LUSC, the genes that were highly correlated with CX3CL1 were not enriched for any biological processes or signalling pathways. Based on the data of the present study, it was hypothesised that CX3CL1 may serve as a prognostic marker for LUAD.
| S-EPMC6507390 | biostudies-literature
Project description:Cancer stem cell (CSC) properties have been recently proposed to explain tumor carcinogenesis and multidrug resistance in several human cancers, including non-small cell lung cancer (NSCLC). The present study examined the protein expression of three CSC-associated markers, namely ATP binding cassette subfamily B member 1 (ABCB1), aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and cluster of differentiation (CD) 44, by immunohistochemistry in 194 NSCLC patients who underwent complete resection of NSCLC tumors. The association between the expression of these proteins and patient prognosis was evaluated to clarify the prognostic significance of CSC-associated markers in NSCLC patients. Positive staining for ABCB1 demonstrated a trend toward worse survival compared with negative staining in stage I-III NSCLC. Negative staining for ALDH1 or CD44 exhibited a trend toward worse survival compared with positive staining in stage I-III NSCLC. It was observed that patients with stage I lung adenocarcinoma (ADC) showing positivity for ABCB1 expression had significantly poorer survival than those with negative ABCB1 staining (P=0.03). Furthermore, stage I ADC patients with wild-type epidermal growth factor receptor (EGFR) who exhibited positive staining for ABCB1 had significantly shorter disease-free survival (DFS) compared with patients with negative staining for ABCB1 (P<0.01). Analyses by univariate and multivariate Cox proportional hazards models revealed that ABCB1-positive staining was significantly associated with DFS and was an independent prognostic factor (hazard ratio, 3.49; P<0.05) in these patients. These results suggest that ABCB1 protein expression is useful for predicting prognosis and selecting patients for post-operative therapy in stage I lung ADC patients, particularly those harboring wild-type EGFR.
| S-EPMC5494850 | biostudies-other
Project description:ObjectivesWe investigated the influence of the preoperative haemoglobin A1c (HbA1c) value on the prognosis and pathology of patients with lung adenocarcinoma who underwent surgery.MethodsWe reviewed the medical records of 400 lung adenocarcinoma patients who underwent lobectomy with mediastinal lymph node dissection between 2009 and 2013 using a prospectively maintained database. We stratified 400 patients into 4 groups according to the preoperative HbA1c value as follows: HbA1c ≤ 5.9 (n = 296), 6.0 ≤ HbA1c ≤ 6.9 (n = 70), 7.0 ≤ HbA1c ≤ 7.9 (n = 21) and HbA1c ≥ 8.0 (n = 12). We compared the recurrence-free survival and overall survival (OS) among these 4 groups. Univariate and multivariate analyses were performed to identify the risk factors for recurrence.ResultsThe median follow-up period was 61.2 months. On comparing the recurrence-free survival and OS rates among these 4 groups, we found that these rates among patients in the HbA1c ≥ 8.0 group were significantly poorer compared with the other 3 groups (5-year recurrence-free survival: HbA1c ≤ 5.9, 70.4%; 6.0 ≤ HbA1c ≤ 6.9, 69.7%; 7.0 ≤ HbA1c ≤ 7.9, 70.7%; ≥8.0 HbA1c, 18.8%; P = 0.002; and 5-year OS: HbA1c ≤ 5.9, 88.7%; 6.0 ≤ HbA1c ≤ 6.9, 80.6%; 7.0 ≤ HbA1c ≤ 7.9, 90.2%; ≥8.0 HbA1c, 66.7%; P = 0.046). Patients in the HbA1c ≥ 8.0 group had significantly more tumours with vascular invasion (P = 0.041) and experienced distant metastasis significantly more often (P = 0.028) than those with other values. A multivariate analysis revealed that preoperative HbA1c ≥ 8.0 [hazard ratio (HR) 2.33; P = 0.026] and lymph node metastasis (HR 3.94; P < 0.001) were significant independent prognostic factors for recurrence.ConclusionsOur results revealed that preoperative HbA1c ≥ 8.0 is associated to poor prognosis due to the occurrence of distant metastasis and we should carefully follow these patients after surgery.Clinical registration numberHyogo Cancer Center, G-57.
| S-EPMC8691722 | biostudies-literature
Project description:Objective: Pancreatic adenocarcinoma (PAAD) is a common malignant tumor worldwide. S100 family (S100s) is wildly involved in regulating the occurrence, development, invasion, metastasis, apoptosis, and drug resistance of many malignant tumors. However, the expression pattern, prognostic value, and oncological role of individual S100s members in PAAD need to be elucidated. Methods: The transcriptional expression levels of S100s were analyzed through the Oncomine and GEPIA, respectively. The protein levels of S100s members in PAAD were studied by Human Protein Atlas. The correlation between S100 mRNA expression and overall survival and tumor stage in PAAD patients was studied by GEPIA. The transcriptional expression correlation and gene mutation rate of S100s members in PAAD patients were explored by cBioPortal. The co-expression networks of S100s are identified using STRING and Gene MANIA to predict their potential functions. The correlation of S100s expression and tumor-infiltrating immune cells was tested by TIMER. Pathway activity and drug target analyzed by GSCALite. Results: 13 S100s members were upregulated in PAAD tissues. 15 S100s members were associated with TP53 mutation. Expression levels of S100A3/A5/A6/A10/A11/A14/A16/B/P/Z were significantly correlated with the pathological stage. Prognosis analysis demonstrated that PAAD patients with low mRNA levels of S100A1/B/Z or high levels of S100A2/A3/A5/A10/A11/A14/A16 had a poor prognosis. Immuno-infiltration analysis showed that the mRNA levels of S100A10/A11/A14/A16 were correlated with the infiltration degree of macrophages in PAAD. Drug sensitivity analysis showed that PAAD expressing high levels of S100A2/A6/A10/A11/A13/A14/A16 maybe resistant to small molecule drugs. Conclusion: This study identifies the clinical significance and biological functions of the S100s in PAAD, which may provide novel insights for the selection of prognostic biomarkers.
| S-EPMC8595214 | biostudies-literature
Project description:Gastric cancer (GC) is the leading malignancy in the digestive system. Versican is a ubiquitous component of the extracellular matrix and has a role in tumor progression. We aim to examine the expression of Versican in GC and the relationship between Versican levels and patient survival. We detected the mRNA expression of Versican in tumorous pairs and adjacent normal tissues (ANTs) of 78 GC patients by quantitative real-time polymerase chain reaction. The protein expression of Versican in 101 cases of matched GC and ANT, as well as in 27 intraepithelial neoplastic (IN) samples, was evaluated by immunohistochemistry. We analyzed the correlation between Versican levels and clinical outcomes. Finally, we performed CCK-8 cell counting assay and transwell assay in GC cell lines. Versican mRNA expression was significantly greater in tumor tissues (P<0.001) than in ANT. Versican was majorly expressed in the stroma surrounding tumor epithelium and minorly some areas of tumor epithelium. The Versican expression level was higher in GC than in ANT (P=0.004), but no significant difference was observed between ANT and IN (P=0.517). The Versican mRNA and protein levels were consistent in GC. High Versican mRNA and protein expression correlated with greater tumor invasion depth (P=0.030, P=0.027). Univariate and multivariate analysis revealed that patients with high Versican mRNA expression exhibited poor disease-specific survival (P<0.001). In vitro experiments showed that Versican overexpression promoted cell proliferation and invasion. Our data indicate that Versican may be a novel prognostic indicator in GC and may be a potential target for clinical diagnosis.
| S-EPMC4670962 | biostudies-other
Project description:BackgroundNumerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD.MethodsThe data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature. Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD.ResultsOverall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment.ConclusionsThe key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.
| S-EPMC8987830 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is a highly mortal cancer. Tertiary lymphoid structures (TLS) are ectopic lymphoid organs with similar morphological and molecular characters to secondary lymphoid organ. The aim of this study is to investigate the prognostic effect of a gene signature associated with TLSs, including B-cell-specific genes.MethodsClinical data of 515 LUAD patients in the TGCA cohort were used to examine the relationship of TLS signature with immune microenvironment, tumor mutational burden (TMB), and driver gene mutations. Patients were divided into the TLS signature high group and TLS signature low group, and comparative analysis of survival and its influencing factors between the two groups was performed. The resulting data were then validated in the GSE37745 cohort.ResultsTLS signature high group had significantly better overall survival (OS) and progression-free interval (PFI) as well as significantly higher infiltration of immune cell subsets, cancer immune cycle (CIC) signature except for immunogram score2 (IGS2), and expression of major checkpoint genes than the TLS signature low group. Notably, while TLS signature was not markedly associated with TMB and mutation frequencies of driver genes, there were significant differences in overall survival of patients with given mutation status of EGFR, KRAS, BRAF and TP53 genes between the TLS signature high and low groups.ConclusionThis study provided evidence that LUAD patients with high TLS signature had a favorable immune microenvironment and better prognosis, suggesting that TLS signature is an independent positive prognostic factor for LUAD patients.
| S-EPMC8352557 | biostudies-literature