GCC2 as a New Early Diagnostic Biomarker for Non-Small Cell Lung Cancer.
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ABSTRACT:
SUBMITTER: Jeong H
PROVIDER: S-EPMC8582534 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.
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Project description:Accumulating evidence has indicated that differentially expressed noncoding circular RNAs (circRNAs) play essential roles in the occurrence and development of various types of cancer. Here, we aimed to identify and explore the diagnostic value of hsa_circ_0003026 (named circUSP10) in patients with early non-small-cell lung cancer (NSCLC). The differentially expressed circRNAs were screened from the microarray-based assay of human NSCLC tissues and their corresponding noncancerous tissues, and the candidate circRNAs were further verified in patients with NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Circulating circUSP10 was isolated from whole blood of healthy people and patients with NSCLC and was detected by RT-qPCR. In addition, the diagnostic value of circUSP10 in early NSCLC was evaluated by receiver operating characteristic (ROC) curve analysis. We found that circUSP10 was upregulated in tumor tissues from patients with early NSCLC and associated with tumor size and tumor-node-metastasis (TNM) stage. Importantly, circUSP10 was obviously upregulated in the whole blood of patients with NSCLC. Additionally, whole blood-derived circUSP10 showed good diagnostic performance for screening early NSCLC and was relatively stable in blood under adverse conditions. These findings demonstrate that circUSP10 may act as a novel biomarker for the diagnosis of early-stage NSCLC, suggesting the potential of circUSP10 in RNA-based therapy for cancer.
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Project description:We performed a series of bioinformatics analysis on a set of important gene expression data with 76 samples in early stage of non-small cell lung cancer, including 40 adenocarcinoma samples, 16 squamous cell carcinoma samples and 20 normal samples. In order to identify the specific markers for diagnosis, we compared the two subtypes with the normal samples respectively to determine the gene expression characteristics. Through the multi-dimensional scaling classification, we found that the samples were clustered well according to the disease cases. Based on the classification results and using empirical Bayes moderation and treat method, 486 important genes associated with the disease were identified. We constructed gene functions and gene pathways to verify our result and explain the pathogenicity factor and process. We generated a protein-protein interaction network based on the mutual interaction between the selected genes and found that the top thirteen hub genes were highly associated with lung cancer or some other cancers including five newly found genes through our method. The results of this study indicated that contrast on the gene expression between different subtypes and normal samples provides important information for the detection of non-small cell lung cancer and helps exploration of the disease pathogenesis.
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Project description:Lung cancer is the most common leading cause of cancer-related death worldwide. Late diagnosis contributes to a high mortality rate and poor survival of this cancer. In our previous study, we found that IDH2 polymorphism rs11540478 is a risk factor for lung cancer. Here, we examined IDH2 protein expression in culture medium in which two non-small-cell lung cancer (NSCLC) cell lines, H460 and A549, were growing. We found that the IDH2 protein was elevated in the culture supernatant fraction in a time- and cell number-dependent manner. Next, we used ELISA methods to examine IDH2 protein level in serum from patients with NSCLC and healthy controls. We found that IDH2 protein levels in serum could distinguish NSCLC patients from healthy controls with an AUC (area under the curve) of 0.83 (95% confidence interval = 0.79-0.88). The IDH2 level was decreased in serum from NSCLC postsurgical patients compared with the paired presurgical serum. High serum IDH2 levels appear to correlate with poor survival in patients with NSCLC. These results suggest that IDH2 levels in the serum could be a new effective biomarker for the diagnosis and prognosis of NSCLC.
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Project description:Lung cancer is the leading cause of cancer death and its incidence is ranked high in men and women worldwide. Non-small-cell lung cancer (NSCLC) adenocarcinoma is one of the most frequent histological subtypes of lung cancer. The aberration profile and the molecular mechanism driving its progression are the key for precision therapy of lung cancer, while the screening of biomarkers is essential to the precision early diagnosis and treatment of the cancer. In this work, we applied a bioinformatics method to analyze the dysregulated interaction network of microRNA-mRNA in NSCLC, based on both the gene expression data and the microRNA-gene regulation network. Considering the properties of the substructure and their biological functions, we identified the putative diagnostic biomarker microRNAs, some of which have been reported on the PubMed citations while the rest, that is, miR-204-5p, miR-567, miR-454-3p, miR-338-3p, and miR-139-5p, were predicted as the putative novel microRNA biomarker for the diagnosis of NSCLC adenocarcinoma. They were further validated by functional enrichment analysis of their target genes. These findings deserve further experimental validations for future clinical application.
| S-EPMC5494096 | biostudies-literature
Project description:BackgroundNon-small cell lung cancer (NSCLC) is leading cause of cancer related death and the survival rate for patients with NSCLC remain poor so early diagnosis of NSCLC represents the best opportunity for cure. Cell-free DNA (cf-DNA) is extracellular nucleic acids found in cell-free plasma/serum of humans, given the recent approval of a liquid biopsy in lung cancer, the use of circulating tumor DNA as a novel non-invasive diagnostic and prognostic biomarker is promising.ObjectivesStudying whether the concentrations of circulating Cell Free DNA in serum can be used as a diagnostic and prognostic biomarker for NSCLC patients.MethodThis study was carried out on 140 subjects included 60 patients with non small cell lung cancer,40 patients with Chronic Obstructive Pulmonary Disease (COPD) and 40 healthy controls. Quantitative analysis of serum circulating cf-DNA was done b y AlU-based quantitative real time PCR. Serum level of CEA was measured by ELISA.ResultsNSCLC patients demonstrated significantly higher values of each of ALU 215, ALU 247, and DNA integrity than both COPD patients and controls. On ROC curve analysis, the total accuracy of ALU 247, ALU 115, DNA integrity (92.1%, 83.6%, 56.4%) at cutoff points (325, 565 & 0.48) respectively. On combining both DNA integrity and CEA, improved sensitivity to 93.3% was noted. For NSCLC patients, ALU 115 & ALU 247 increased significantly with more advanced stage and highest level was noticed in metastatic patients. Regarding survival there was better overall survival among patients with low DNA integrity.ConclusionSerum cf-DNA concentrations and integrity index may be valuable tool in early diagnosis of NSCLC and prediction of prognosis of those patients.
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Project description:Distal-less homeobox 6 antisense RNA 1 (DLX6-AS1) is upregulated in various solid tumors and serves a critical role in the tumorigenesis of cancer. However, to the best of our knowledge, the expression of circulating DLX6-AS1 and its role in the diagnosis of non-small cell lung cancer (NSCLC) have not been previously clarified. The aim of the present study was to investigate the expression and clinical significance of circulating DLX6-AS1 using reverse transcription-quantitative PCR in serum and exosomes derived from patients with NSCLC and healthy donors. The diagnostic value of circulating DLX6-AS1 was identified by receiver operating characteristic curve (ROC) analysis. First, it was revealed that the expression levels of DLX6-AS1 were significantly increased in tumor tissues compared with in adjacent normal tissues. In addition, DLX6-AS1 was highly expressed in NSCLC cell lines compared with in BEAS-2B cells. DLX6-AS1-knockdown inhibited cell proliferation and migration in vitro. It was subsequently demonstrated that the serum DLX6-AS1 level was significantly higher in patients with NSCLC compared with in healthy controls. Additionally, the higher DLX6-AS1 expression was associated with advanced disease stage, positive lymph node metastasis and poor tumor differentiation of NSCLC. ROC analysis demonstrated that the sensitivity and specificity of DLX6-AS1 were higher than those of CYFRA21-1, which is a serum marker for NSCLC. Finally, exosomal DLX6-AS1 expression was increased in patients with NSCLC compared with in healthy controls. The present data implied that circulating DLX6-AS1 was mainly incorporated into exosomes, providing a novel potential diagnostic marker for NSCLC.
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Project description:BackgroundNon-small-cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC.MethodsWe assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4-knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analyses. The significance of autophagy-related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechanisms behind RBBP4-mediated autophagic cell death in NSCLC.ResultsRBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy-related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3-MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell-injected nude mice, elevating autophagy-related protein levels and inducing apoptosis and necrosis in tumor tissues.ConclusionIn NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target.
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Project description:Survivin inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localisation of survivin predicts survival of 48 patients with resected non-small-cell lung cancer (NSCLC). Patients with nuclear staining of survivin had significantly worse survival (relative risk: 3.9, P=0.02). Therefore, survivin may be a biomarker for NSCLC.
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Project description:Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription-quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.
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