DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen J
PROVIDER: S-EPMC8636112 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:PurposeThe dysregulation of arrestin domain containing 3 (ARRDC3) has an important effect on oncogenesis and tumor progression in many cancers, including renal cell carcinoma and breast cancer. However, the role of ARRDC3 in ovarian cancer (OC) has not been reported.MethodsThe present study explored the diagnostic and prognostic roles of ARRDC3 in ovarian cancer using GEPIA, ONCOMINE, GEO, and Kaplan-Meier Plotter databases for training and validation. Then, we conducted a stratified analysis for clinicopathological factors using Kaplan-Meier Plotter and GEPIA databases. To further explore the mechanisms, we also used the MIST database to visualize the protein-protein interaction network of ARRDC3 associated with OC. The gene-gene interaction network was visualized by GeneMANIA plugin in Cytoscape 3.8.0 software, and the associated co-expression genes of ARRDC3 were analyzed by the cBioPortal database. The 100 top co-expression genes chosen for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used by the DAVID website.ResultsA significant difference in ARRDC3 mRNA expression was found between OC and normal ovary tissues. ARRDC3 could potentially be implicated in the diagnosis of OC. A high ARRDC3 mRNA expression level was associated with poor overall survival and progression-free survival. However, no significance was reported in respect to post progression survival. Except for histology, which had no prognostic value for PPS in stratified analysis, stratified analysis of other factors had prognostic value for OS, PFS, and PPS. Interestingly, we found a positive correlation between ARRDC3 expression and CD8+ T cells, macrophages, neutrophils, and dendritic cells, indicating that ARRDC3 might be associated with immune infiltration of these immune cells. Co-expression genes enrichment analysis found that they were involved in the Renin-angiotensin system pathway.ConclusionDifferentially expressed ARRDC3 might be a potential prognostic and diagnostic marker in Ovarian Cancer.
| S-EPMC7997607 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD), a major and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to assess key genes and to develop a prognostic signature for the patient therapy with LUAD.MethodRNA expression profile and clinical data from 522 LUAD patients were accessed and downloaded from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were extracted and analyzed between normal tissues and LUAD samples. Then, a 14-DEG signature was developed and identified for the survival prediction in LUAD patients by means of univariate and multivariate Cox regression analyses. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential biological functions and pathways of these DEGs.ResultsTwenty-two out of 5924 DEGs in the TCGA dataset were screened and associated with the overall survival (OS) of LUAD patients. 14CID="C008" value=" "DEGs were finally selected and included in our development and validation model by risk score analysis. The ROC analysis indicated that the specificity and sensitivity of this profile signature were high. Further functional enrichment analyses indicated that these DEGs might regulate genes that affect the function of release of sequestered calcium ion into cytosol and pathways that associated with vibrio cholerae infection.ConclusionOur study developed a novel 14-DEG signature providing more efficient and persuasive prognostic information beyond conventional clinicopathological factors for survival prediction of LUAD patients.
| S-EPMC7769675 | biostudies-literature
Project description:BackgroundAlthough it has a poor prognosis, patients with lung adenocarcinoma (LUAD) have a relatively higher 5-year survival period. Thus, it is necessary to identify effective prognostic markers to evaluate the effect of early treatment. RS1 gene encodes retinoschisin, a key protein in congenital retinoschisis, while few studies have been reported on the association between RS1 and cancer prognosis.MethodsWe performed bioinformatic analyses based on the data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases to demonstrate the expression level of RS1 was related to the LUAD prognosis and our findings were verified in-vitro and clinical samples. Then, we explored the potential mechanism of how RS1 expression influenced the prognosis of LUAD.ResultsCompared with normal tissues, the RS1 expression was significantly lower in tumor tissues. The Multivariate Cox regression model showed that RS1 could be used as an independent prognostic indicator. Furthermore, we found significant differences in immune cell infiltration between RS1 high and low expression groups, and the proteasome pathway was found enriched in RS1 low expression samples.ConclusionIn conclusion, our study suggests that RS1 is a novel prognostic biomarker for LUAD. Differences in immune cell infiltration and signaling pathways may contribute to the poor prognosis of LUAD caused by low RS1 expression.
| S-EPMC9200886 | biostudies-literature
Project description:Currently, there is no reliable biomarker to clinically predict the prognosis of lung adenocarcinoma (ADC). The receptor-tyrosine-kinase like orphan receptor 1 (ROR1) is reported to be overexpressed and associated with poor prognosis in several tumors. This study aimed to examine the expression of ROR1 and evaluate its prognostic significance in human lung ADC patients. In this present study, Western blot analysis and immunohistochemistry were performed to characterize expression of ROR1 protein in lung ADC patients. The results revealed that ROR1 protein expression was significantly higher in lung ADC tissues than that in their adjacent non-tumor tissues. Patients at advanced stages and those with positive lymph node metastasis expressed higher level of ROR1 (P < 0.001). Moreover, Chi-square test showed that ROR1 expression was correlated to gender (P = 0.028), the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) staging system and lymph node metastasis (P < 0.001). Kaplan-Meier survival analysis indicated an association of high ROR1 expression with worse overall survival (OS) in lung ADC patients (P < 0.001). Multivariate COX regression analysis further confirmed that ROR1 is an independent prognostic predictor (P < 0.001, HR = 4.114, 95% CI: 2.513-6.375) for OS. Therefore, ROR1 expression significantly correlates with malignant attributes of lung ADC and it may serve as a novel prognostic marker in lung ADC patients.
| S-EPMC5103212 | biostudies-literature
Project description:The incidence of lung adenocarcinoma (LUAD), the most common subtype of lung cancer, continues to make lung cancer the largest cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been shown to have a significant role in both the onset and progression of lung cancer. In this study, we aimed to investigate the clinical significance and underlying mechanism of lncRNA NPSR1-AS1 (NPSR1-AS1) in LUAD. First, we performed an analysis on TCGA and identified 229 differentially expressed lncRNAs (DELs) (including 216 upregulated lncRNAs and 13 downregulated lncRNAs). Then, we carried out a screening of the lncRNAs associated with survival, and a total of 382 survival-related lncRNAs were found. 15 survival-related DELs were identified. Among them, our attention focused on NPSR1-AS1. We found that the expression of NPSR1-AS1 was much higher in LUAD specimens compared to nontumor tissues. According to the results of the ROC assays, high NPSR1-AS1 expression had an AUC value of 0.904 for LUAD, with a 95% confidence interval ranging from 0.881 to 0.927. The expression of NPSR1-AS1 was shown to be significantly elevated in a wide variety of cancers, according to the findings of a pancancer investigation. Functional enrichment analysis confirmed that NPSR1-AS1 was involved in LUAD progression via regulating several tumor-related pathways. Patients with high levels of NPSR1-AS1 expression were shown to have a shorter disease-specific survival (DSS) or overall survival (OS) than those with low levels of NPSR1-AS1 expression, according to the findings of a clinical investigation. It was determined by multivariate analysis that NPSR1-AS1 expressions served as an independent prognostic factor for the overall survival of LUAD patients. The results of immune cell infiltration revealed that the expressions of NPSR1-AS1 were negatively associated with CD8 T cells, pDC, cytotoxic cells, mast cells, iDC, neutrophils, NK CD56dim cells, DC, Th17 cells, Tgd, and macrophages, while they were positively associated with NK CD56bright cells and B cells. Overall, our findings revealed that NPSR1-AS1 could serve as a potential biomarker to assess the clinical outcome and immune infiltration level in LUAD.
| S-EPMC9588325 | biostudies-literature
Project description:BackgroundSLC15A family members are known as electrogenic transporters that take up peptides into cells through the proton-motive force. Accumulating evidence indicates that aberrant expression of SLC15A family members may play crucial roles in tumorigenesis and tumor progression in various cancers, as they participate in tumor metabolism. However, the exact prognostic role of each member of the SLC15A family in human lung cancer has not yet been elucidated.Materials and methodsWe investigated the SLC15A family members in lung cancer through accumulated data from TCGA and other available online databases by integrated bioinformatics analysis to reveal the prognostic value, potential clinical application and underlying molecular mechanisms of SLC15A family members in lung cancer.ResultsAlthough all family members exhibited an association with the clinical outcomes of patients with NSCLC, we found that none of them could be used for squamous cell carcinoma of the lung and that SLC15A2 and SLC15A4 could serve as biomarkers for lung adenocarcinoma. In addition, we further investigated SLC15A4-related genes and regulatory networks, revealing its core molecular pathways in lung adenocarcinoma. Moreover, the IHC staining pattern of SLC15A4 in lung adenocarcinoma may help clinicians predict clinical outcomes.ConclusionSLC15A4 could be used as a survival prediction biomarker for lung adenocarcinoma due to its potential role in cell division regulation. However, more studies including large patient cohorts are required to validate the clinical utility of SLC15A4 in lung adenocarcinoma.
| S-EPMC8217884 | biostudies-literature
Project description:Hyaluronic acid-mediated motility receptor (HMMR), a tumor-related gene, plays a vital role in the occurrence and progression of various cancers. This research is aimed to reveal the effect of HMMR in lung adenocarcinoma (LUAD). We first obtained the gene expression profiles and clinical data of patients with LUAD from The Cancer Genome Atlas (TCGA) database. Then, based on the TCGA cohort, the HMMR expression difference between LUAD tissues and nontumor tissues was detected and verified with public tissue microarrays (TMAs), clinical LUAD specimen cohort, and Gene Expression Omnibus (GEO) cohort. Logistic regression analysis and chi-square test were adopted to study the correlation between HMMR expression and clinicopathological parameters. The effect of HMMR expression on survival was evaluated by Kaplan-Meier survival analysis and using the Cox regression model. Furthermore, Gene Set Enrichment Analysis (GSEA) was utilized to screen out signaling pathways related to LUAD and the co-expression analysis was employed to build the protein-protein interaction (PPI) network. The HMMR expression level in LUAD tissues was dramatically higher than that in nontumor tissues. Logistic regression analysis and chi-square test demonstrated that the high HMMR expression in LUAD has relation with gender, pathological stage, T classification, lymph node metastasis, and distant metastasis. The Kaplan-Meier curve suggested a poor prognosis for LUAD patients with high HMMR expression. Multivariate analysis implied that the high HMMR expression was a vital independent predictor of poor overall survival (OS). GSEA indicated that a total of 15 signaling pathways were enriched in samples with the high HMMR expression phenotype. The PPI network gave 10 genes co-expressed with HMMR. HMMR may be an oncogene in LUAD and is expected to become a potential prognostic indicator and therapeutic target for LUAD.
| S-EPMC8435795 | biostudies-literature
Project description:BackgroundAs a common pathological type of lung cancer, lung adenocarcinoma (LUAD) is mainly treated by surgery, chemotherapy, targeted therapy and radiotherapy. Although a relatively mature treatment system has been established, there are few studies on the microenvironment of LUAD.Material and methodsThe immune and stromal scores of patients from the LUAD cohort in the TCGA database were obtained by using ESTIMATE. The relationship of immune and stromal scores with the clinicopathological characteristics and overall survival of LUAD patients was assessed by R. GO, KEGG and Cox regression analyses were employed to analyze intersecting genes and to identify reliable prognostic markers. The identified genes were also analyzed in the GEPIA database to assess their correlations with survival, and these relationships were verified with the Kaplan-Meier Plotter database.ResultsThe immune score was related to the survival time and tumor topography of LUAD patients. There was a significant correlation between stromal score and tumor metastasis. Through multivariate analysis, stage (HR = 1.640, 95% CI = 1.019-2.642, P = 0.042) and risk score (HR = 1.036, 95% CI = 1.026-1.046, P < 0.001). The genes (ARHGAP15, BTLA, CASS4, CLECL1, FAM129C, STAP1, TESPA1, and S100P) showed credible prognostic value in LUAD patients in TCGA through GEPIA database online analysis and verification in the Kaplan-Meier plotter database.ConclusionsIn the microenvironment of lung adenocarcinoma, the differentially expressed genes screened by immune score and stromal score have certain value in evaluating the survival/prognosis of patients, as well as the invasion and progression of tumors.
| S-EPMC7724272 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. LncRNA-AL139385.1 (ENSG00000275880) is a novel lncRNA that is abnormally expressed in various cancer types including LUAD. However, the underlying biological function and potential mechanisms of AL139385.1 driving the progression of LUAD remain unclear. In this study, we investigated the role of AL139385.1 in LUAD and found that DNA hypomethylation was positively correlated with AL139385.1 expression in LUAD. Moreover, we uncover that the expression of AL139385.1 in LUAD tissues was significantly higher than that of AL139385.1 expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher AL139385.1 expression correlated with adverse overall survival and progression-free survival. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) value of AL139385.1 was 0.808. Correlation analysis showed that AL139385.1 expression was associated with immune infiltration in LUAD. We also found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of AL139385.1 significantly inhibited cell proliferation and migration abilities of LUAD. Finally, we constructed a ceRNA network that includes hsa-miR-532-5p and four mRNAs (GALNT3, CYCS, EIF5A, and ITGB4) specific to AL139385.1 in LUAD. Subsequent Kaplan-Meier survival analysis suggested that polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), cytochrome c, somatic (CYCS), eukaryotic translation initiation factor 5A (EIF5A), and integrin subunit beta 4 (ITGB4), were potential prognostic biomarkers for patients with LUAD. In conclusion, this finding provides possible mechanisms underlying the abnormal upregulation of AL139385.1 as well as a comprehensive view of the AL139385.1-mediated competing endogenous RNAs (ceRNA) network in LUAD, thereby highlighting its potential role in diagnosis and therapy.
| S-EPMC9149219 | biostudies-literature
Project description:BackgroundEnhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. However, the role of eRNAs in lung adenocarcinoma (LUAD) remains largely unclear. Thus, a comprehensive analysis was constructed to identify the key eRNAs, and to explore the clinical utility of the identified eRNAs in LUAD.MethodsFirst, LUAD expression profile data from the Cancer Genome Atlas (TCGA) dataset and eRNA-relevant information were integrated for Kaplan-Meier survival analysis and Spearman's correlation analysis to filtered the key candidate eRNAs that was associated with survival rate and their target genes in LUAD. Then, the key eRNA was selected for subsequent clinical correlation analysis. KEGG pathway enrichment analyses were undertaken to explore the potential signaling pathways of the key eRNA. Data from the human protein atlas (HPA) database were used to validate the outcomes and the quantitative real time-polymerase chain reaction (qRT-PCR) analysis was conducted to measure eRNA expression levels in tumor tissues and paired normal adjacent tissues from LUAD patients. Finally, the eRNAs were validated in pan-cancer.ResultsAs a result, TBX5-AS1 was identified as the key eRNA, which has T-box transcription factor 5 (TBX5) as its regulatory target. KEGG analysis indicated that TBX5-AS1 may exert a vital role via the PI3K/AKT pathway, Ras signaling pathway, etc. Additionally, the qRT-PCR results and the HPA database indicated that TBX5-AS1 and TBX5 were significantly downregulated in tumour samples compared to matched-adjacent pairs. The pan-cancer validation results showed that TBX5-AS1 was associated with survival in four tumors, namely, adrenocortical carcinoma (ACC), LUAD, lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). Correlations were found between TBX5-AS1 and its target gene, TBX5, in 26 tumor types.ConclusionCollectively, our results indicated that TBX5-AS1 may be a potential prognostic biomarker for LUAD patients and promote the targeted therapy of LUAD.
| S-EPMC8268367 | biostudies-literature