Systematic assessment of the clinicopathological prognostic significance of tissue cytokine expression for lung adenocarcinoma based on integrative analysis of TCGA data.
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ABSTRACT:
SUBMITTER: Dong Y
PROVIDER: S-EPMC6474906 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:Lung adenocarcinoma (LUAD) is a common malignant tumor with a poor prognosis. Recent studies have found that angiopoietin-like 4 (ANGPTL4) is abnormally expressed in many tumors, so it can serve as a potential prognostic marker and therapeutic target. However, its prognostic value in LUAD remains unclear. We downloaded RNA sequence data for LUAD from The Cancer Genome Atlas (TCGA) database, methylation data from the University of California Santa Cruz genome database, and clinical information. R software (version 4.1.1) was applied to analyze the ANGPTL4 expression in LUAD and nontumor samples, and the correlation with clinical characteristics to assess its prognostic and diagnostic value. In addition, we analyzed the relationship between the ANGPTL4 expression and methylation levels. Tumor IMmune Estimation Resource (TIMER) tool was taken for immune infiltration analysis, and two Gene Expression Omnibus (GEO) datasets were combined for meta-analysis. Finally, differentially expressed genes (DEGs) related to ANGPTL4 were analyzed to clarify its function. As shown in our results, ANGPTL4 was upregulated in LUAD and was an independent risk factor for the diagnosis and prognosis of LUAD. The general methylation level and eight ANGPTL4 methylation sites were significantly negatively correlated with the ANGPTL4 expression. Furthermore, we found that B cell infiltration was negatively correlated with ANGPTL4 expression and was an independent risk factor. Meta-analysis showed that the high expression of ANGPTL4 was closely associated with a poor prognosis. 153 DEGs, including the matrix metalloproteinase family, the chemokines subfamily, and the collagen family, were correlated with ANGPTL4. In this study, we found that ANGPTL4 was significantly elevated in LUAD and was closely associated with the development and poor prognosis of LUAD, suggesting that ANGPTL4 may be a prognostic biomarker and a potential therapeutic target for LUAD.
| S-EPMC9568294 | biostudies-literature
Project description:On the basis of our recent findings of oncogenic KRAS-induced interleukin-8 (IL-8) overexpression in non-small cell lung cancer, we assessed the clinicopathological and prognostic significances of IL-8 expression and its relationship to KRAS mutations in lung adenocarcinomas.IL-8 expression was examined by quantitative RT-PCR using 136 of surgical specimens from lung adenocarcinoma patients. The association between IL-8 expression, clinicopathological features, KRAS or EGFR mutation status and survival was analysed.IL-8 was highly expressed in tumours from elderly patients or smokers and in tumours with pleural involvement or vascular invasion. In a non-smokers' subgroup, IL-8 level positively correlated with age. IL-8 was highly expressed in tumours with KRAS mutations compared with those with EGFR mutations or wild-type EGFR/KRAS. Lung adenocarcinoma patients with high IL-8 showed significantly shorter disease-free survival (DFS) and overall survival (OS) than those with low IL8. DFS and OS were significantly shorter in the patients with mutant KRAS/high IL-8 than in those with wild-type KRAS/low IL-8. Cox regression analyses demonstrated that elevated IL-8 expression correlated with unfavourable prognosis.Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is a potent prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS-driven adenocarcinoma.
| S-EPMC3992490 | biostudies-other
Project description:BackgroundThe clinicopathological and prognostic significance of SRY-box transcription factor 9 (SOX9) expression in gastric cancer (GC) patients is still controversial. Our aim is to investigate the clinicopathological and prognostic value of SOX9 expression in GC patients.MethodsA systemic literature search and meta-analysis were used to evaluate the clinicopathological significance and overall survival (OS) of SOX9 expression in GC patients. The Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between SOX9 expression and OS of stomach adenocarcinoma (STAD) patients.ResultsA total of 11 articles involving 3,060 GC patients were included. In GC patients, the SOX9 expression was not associated with age [odds ratio (OR) = 0.743, 95% CI = 0.507-1.089, p = 0.128], sex (OR = 0.794, 95% CI = 0.605-1.042, p = 0.097), differentiation (OR = 0.728, 95% CI = 0.475-1.115, p = 0.144), and lymph node metastasis (OR = 1.031, 95% CI = 0.793-1.340, p = 0.820). SOX9 expression was associated with depth of invasion (OR = 0.348, 95% CI = 0.247-0.489, p = 0.000) and TNM stage (OR = 0.428, 95% CI = 0.308-0.595, p = 0.000). The 1-year OS (OR = 1.507, 95% CI = 1.167-1.945, p = 0.002), 3-year OS (OR = 1.482, 95% CI = 1.189-1.847, p = 0.000), and 5-year OS (OR = 1.487, 95% CI = 1.187-1.862, p = 0.001) were significantly shorter in GC patients with high SOX9 expression. TCGA analysis showed that SOX9 was upregulated in STAD patients compared with that in normal patients (p < 0.001), and the OS of STAD patients with a high expression of SOX9 is poorer than that in patients with low expression of SOX9, but the statistical difference is not obvious (p = 0.31).ConclusionSOX9 expression was associated with the depth of tumor invasion, TNM stage, and poor OS of GC patients. SOX9 may be a potential prognostic factor for GC patients but needs further study.Systematic review registrationPROSPERO, ID NUMBER 275712.
| S-EPMC8458960 | 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:BackgroundAT-rich interaction domain 1A (ARID1A) is an essential subunit of the switch/sucrose non-fermentable chromatin remodeling complex and is considered to be a tumor suppressor. The Cancer Genome Atlas (TCGA) molecular classification has deepened our understanding of gastric cancer at the molecular level. This study explored the significance of ARID1A expression in TCGA subtypes of gastric adenocarcinoma.MethodsWe collected 1248 postoperative patients with gastric adenocarcinoma, constructed tissue microarrays, performed immunohistochemistry for ARID1A, and obtained correlations between ARID1A and clinicopathological variables. We then carried out the prognostic analysis of ARID1A in TCGA subtypes. Finally, we screened patients by random sampling and propensity score matching method and performed multiplex immunofluorescence to explore the effects of ARID1A on CD4, CD8, and PD-L1 expression in TCGA subtypes.ResultsSeven variables independently associated with ARID1A were screened out: mismatch repair proteins, PD-L1, T stage, differentiation status, p53, E-cadherin, and EBER. The independent prognostic variables in the genomically stable (GS) subtype were N stage, M stage, T stage, chemotherapy, size, and ARID1A. PD-L1 expression was higher in the ARID1A negative group than in the ARID1A positive group in all TCGA subgroups. CD4 showed higher expression in the ARID1A negative group in most subtypes, while CD8 did not show the difference in most subtypes. When ARID1A was negative, PD-L1 expression was positively correlated with CD4/CD8 expression; while when ARID1A was positive, this correlation disappeared.ConclusionsThe negative expression of ARID1A occurred more frequently in the Epstein-Barr virus and microsatellite instability subtypes and was an independent adverse prognostic factor in the GS subtype. In the TCGA subtypes, ARID1A negative expression caused increased CD4 and PD-L1 expression, whereas CD8 expression appeared independent of ARID1A. The expression of CD4/CD8 induced by ARID1A negativity was accompanied by an increase in PD-L1 expression.
| S-EPMC10501255 | 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:LIM-domain only protein 7 (LMO7) has been suggested to act as a tumor suppressor for murine lung adenocarcinoma, while its splice variant p100 LMO7/#16 is associated with invasion and metastasis of rat AH130W1 cells. However, the importance of LMO7 in human lung cancer is unknown. We investigated LMO7 protein expression by immunohistochemistry in tumor tissues obtained from 57 patients with adenocarcinoma of the lung using a rabbit anti-LMO7 antibody. Signals for LMO7 were localized to the apical surface of the bronchial epithelium and to the cell membranes of pneumocytes in non-cancerous pulmonary tissues, but were noted circumferentially around the plasma membrane of cancer cells in all 57 patients with adenocarcinoma. The LMO7-positive group (24 patients, 42%) showed equivocal to strong expression of LMO7 in more than 50% cancer cells, while the remaining 33 patients (58%) showed LMO7 expression in less than 50% of their cancer cells. The latter group had significantly more advanced disease than the LMO7-positive group with regard to T factor (p=0.011), nodal involvement (p=0.026) and p-stage (p=0.010; Ļ(2) test). Multivariate analysis using a logistic regression model showed that LMO7 expression was independently associated with the T factor (p=0.041). Kaplan-Meier analysis showed that a poor prognosis was associated with low expression of LMO7 (p=0.036; log-rank test). Our findings are consistent with earlier observations and demonstrate that LMO7 is inversely correlated with the development and prognosis of human lung adenocarcinoma.
| S-EPMC3440790 | biostudies-literature
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 (Pā<ā0.001), 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: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 cancer is a malignant tumor with the highest incidence and mortality around the world. Recent advances in RNA sequencing technology have enabled insights into long non-coding RNAs (lncRNAs), a previously largely overlooked species in dissecting lung cancer pathology.MethodsIn this study, we used a comprehensive bioinformatics analysis strategy to identify lncRNAs closely associated with lung adenocarcinoma, using the RNA sequencing datasets collected from more than 500 lung adenocarcinoma patients and deposited at The Cancer Genome Atlas (TCGA) database.ResultsDifferential expression analysis highlighted lncRNAs CTD-2510F5.4 and CTB-193M12.5, both of which were significantly upregulated in cancerous specimens. Moreover, network analyses showed highly correlated expression levels of both lncRNAs with those of differentially expressed protein-coding genes, and suggested central regulatory roles of both lncRNAs in the gene co-expression network. Importantly, expression of CTB-193M12.5 showed strong negative correlation with patient survival.ConclusionsOur study mined existing TCGA datasets for novel factors associated with lung adenocarcinoma, and identified a largely unknown lncRNA as a potential prognostic factor. Further investigation is warranted to characterize the roles and significance of CTB-193M12.5 in lung adenocarcinoma biology.
| S-EPMC5824544 | biostudies-literature