Pairwise correlation of genes involved in glucose metabolism: a potential diagnostic marker of cancer?
Ontology highlight
ABSTRACT:
SUBMITTER: Sakharkar MK
PROVIDER: S-EPMC8211569 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Early screening, particularly in blood plasma, has been demonstrated as a promising approach to the diagnosis and prevention of AD. In addition, metabolic dysfunction has been demonstrated to be closely related to AD, which might be reflected in the whole blood transcriptome. Hence, we hypothesized that the establishment of a diagnostic model based on the metabolic signatures of blood is a workable strategy. To that end, we initially constructed metabolic pathway pairwise (MPP) signatures to characterize the interplay among metabolic pathways. Then, a series of bioinformatic methodologies, e.g., differential expression analysis, functional enrichment analysis, network analysis, etc., were used to investigate the molecular mechanism behind AD. Moreover, an unsupervised clustering analysis based on the MPP signature profile via the Non-Negative Matrix Factorization (NMF) algorithm was utilized to stratify AD patients. Finally, aimed at distinguishing AD patients from non-AD groups, a metabolic pathway-pairwise scoring system (MPPSS) was established using multi-machine learning methods. As a result, many metabolic pathways correlated to AD were disclosed, including oxidative phosphorylation, fatty acid biosynthesis, etc. NMF clustering analysis divided AD patients into two subgroups (S1 and S2), which exhibit distinct activities of metabolism and immunity. Typically, oxidative phosphorylation in S2 exhibits a lower activity than that in S1 and non-AD group, suggesting the patients in S2 might possess a more compromised brain metabolism. Additionally, immune infiltration analysis showed that the patients in S2 might have phenomena of immune suppression compared with S1 and the non-AD group. These findings indicated that S2 probably has a more severe progression of AD. Finally, MPPSS could achieve an AUC of 0.73 (95%CI: 0.70, 0.77) in the training dataset, 0.71 (95%CI: 0.65, 0.77) in the testing dataset, and an AUC of 0.99 (95%CI: 0.96, 1.00) in one external validation dataset. Overall, our study successfully established a novel metabolism-based scoring system for AD diagnosis using the blood transcriptome and provided new insight into the molecular mechanism of metabolic dysfunction implicated in AD.
| S-EPMC10298314 | biostudies-literature
Project description:Dysregulation of miRNAs has a fundamental role in the initiation, development and progression of prostate cancer (PCa). The potential of miRNA in gene therapy and diagnostic applications is well documented. To further improve miRNAs' ability to distinguish between PCa and benign prostatic hyperplasia (BPH) patients, nine miRNA (-21, -27b, -93, -141, -205, -221, -182, -375 and let-7a) with the highest reported differentiation power were chosen and for the first time used in comparative studies of serum and prostate tissue samples. Spearman correlations and response operating characteristic (ROC) analyses were applied to assess the capability of the miRNAs present in serum to discriminate between PCa and BPH patients. The present study clearly demonstrates that miR-93 and miR-375 could be taken into consideration as single blood-based non-invasive molecules to distinguish PCa from BPH patients. We indicate that these two miRNAs have six common, PCa-related, target genes (CCND2, MAP3K2, MXI1, PAFAH1B1, YOD1, ZFYVE26) that share the molecular function of protein binding (GO:0005515 term). A high diagnostic value of the new serum derived miR-182 (AUC = 0.881, 95% confidence interval, CI = 0.816-0.946, p < 0.0001, sensitivity and specificity were 85% and 79%, respectively) is also described.
| S-EPMC7460886 | biostudies-literature
Project description:Fine-needle aspiration (FNA) is the most commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. Based on multifunctionality of the endogenous galectin-1, we aimed to assess its status for early diagnosis of thyroid cancer. Immunohistochemistry for galectin-1 and -3 was performed on a clinical series of 69 cases of thyroid lesions. Galectin-1 expression was further examined in two additional tissue microarrays (TMA) composed of 66 follicular adenomas and 66 papillary carcinomas in comparison to galectin-3 and cytokeratin-19 (CK19). In addition, a knockdown of galectin-1 in papillary (TPC-1) and anaplastic (8505C) thyroid cancer cell lines was achieved by lentiviral transduction for in vitro experiments. A murine orthotopic thyroid cancer model was used to investigate tumor growth and metastatic ability. Immunohistochemical analyses of galectin-1 and -3 in the series of 69 cases of thyroid lesions revealed that galectin-1 was completely absent in the epithelial compartment of all benign thyroid lesions. Levels of both galectins significantly increased in the cytoplasmic compartment of malignant thyroid cells. Galectin-1 expression in the TMA yielded an excellent specificity (97%), while galectin-3 and CK19 presented a higher sensitivity (>97%) in discriminating benign from malignant thyroid lesions. In vitro experiments revealed that migration was negatively affected in TPC-1 galectin-1 knockdown (KD) cells, and that proliferation and invasion capacity of 8505C cells decreased after galectin-1 KD. Moreover, an orthotopic mouse model displayed a lower rate of tumor development with galectin-1 KD thyroid anaplastic cancer cells than in the control. Our findings support the introduction of galectin-1 as a reliable diagnostic marker for thyroid carcinomas. Its involvement in cell proliferation, migration, invasion and tumor growth also intimate functional involvement of galectin-1 in the progression of thyroid carcinoma, suggesting its potential as a therapeutic target.
| S-EPMC5564411 | biostudies-other
Project description:PurposeColon cancer is one of the leading causes of death worldwide, and screening of effective molecular markers for the diagnosis is prioritised for prevention and treatment. This study aimed to investigate the diagnostic and predictive potential of genes related to the lipid metabolism pathway, regulated by a protein called sterol-regulatory element-binding transcription Factor 2 (SREBF2), for colon cancer and patient outcomes.MethodsWe used machine-learning algorithms to identify key genes associated with SREBF2 in colon cancer based on a public database. A nomogram was created to assess the diagnostic value of these genes and validated in the Cancer Genome Atlas. We also analysed the relationship between these genes and the immune microenvironment of colon tumours, as well as the correlation between gene expression and clinicopathological characteristics and prognosis in the China Medical University (CMU) clinical cohort.ResultsThree genes, 7-dehydrocholesterol reductase (DHCR7), hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and Ral guanine nucleotide dissociation stimulator-like 1 (RGL1), were identified as hub genes related to SREBF2 and colon cancer. Using the TCGA dataset, receiver operating characteristic curve analysis showed the area under the curve values of 0.943, 0.976, and 0.868 for DHCR7, HSD11B2, and RGL1, respectively. In the CMU cohort, SREBF2 and DHCR7 expression levels were correlated with TNM stage and tumour invasion depth (P < 0.05), and high DHCR7 expression was related to poor prognosis of colon cancer (P < 0.05). Furthermore, DHCR7 gene expression was positively correlated with the abundance of M0 and M1 macrophages and inversely correlated with the abundance of M2 macrophages, suggesting that the immune microenvironment may play a role in colon cancer surveillance. There was a correlation between SREBF2 and DHCR7 expression across cancers in the TCGA database.ConclusionThis study highlights the potential of DHCR7 as a diagnostic marker and therapeutic target for colon cancer.
| S-EPMC10723182 | biostudies-literature
Project description:Glycogen storage diseases (GSDs) belong to the group of inborn errors of carbohydrate metabolism. Hepatic GSDs predominantly involve the liver and most present with hepatomegaly. Biochemically they show known disturbances in glucose and fatty acids metabolism, namely fasting hypoglycaemia and increased triglycerides. Additionally, increased biotinidase (BTD) enzyme activity has been shown to be associated with many GSD types, whereas the mechanism by which BTD enzyme activity is altered remains unknown so far. We aimed to delineate changes in gluconeogenesis and fatty acid synthesis, potentially explaining raised BTD enzyme activity, by using liver (specimens from 2 patients) and serum samples of GSD Ia and GSD IV patients. By expression analysis of genes involved in gluconeogenesis, we ascertained increased levels of phosphoenolpyruvate carboxykinase and fructose-1,6-biphosphatase, indicating an increased flux through the gluconeogenic pathway. Additionally, we found increased gene expression of the biotin-dependent pyruvate and acetyl-CoA carboxylases, providing substrate for gluconeogenesis and increased fatty acid synthesis. We also observed a significant linear correlation between BTD enzyme activity and triglyceride levels in a cohort of GSD Ia patients. The results of this pilot study suggest that enhancement of BTD activity might serve the purpose of providing extra cofactor to the carboxylase enzymes as an adjustment to disturbed glucose and fatty acid metabolism. Future studies involving a higher number of samples should aim at confirming the here proposed mechanism, which extends the application of BTD enzyme activity measurement beyond its diagnostic purpose in suspected GSD, and opens up possibilities for its use as a sensor for increased gluconeogenesis and fatty acid synthesis.
| S-EPMC7802622 | biostudies-literature
Project description:Lung cancer remains one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 20%. One approach to improving survival is the identification of biomarkers to detect early stage disease. In this study, we investigated the potential of the stem cell and progenitor cell marker, Musashi1 (Msi1), as a diagnostic marker and potential therapeutic target for lung cancer. Functional studies in A549 bronchioalveolar carcinoma and NCI-H520 squamous cell carcinoma cells revealed that Msi1 was enriched in spheroid cultures of tumor cells and in the CD133+ cell population. Downregulation of Msi1 by lentivirus-mediated expression of an Msi1 shRNA reduced spheroid colony proliferation. Growth inhibition was associated with reduced nuclear localization of ?-catenin and inhibition of the processing of intracellular Notch. In primary lung cancer, Msi1 protein expression was elevated in 86% of 202 tissue microarray specimens, and Msi1 mRNA was increased in 80% of 118 bronchoscopic biopsies, including metastatic disease, but was rarely detected in adjacent normal lung tissue and in non-malignant diseased tissue. Msi1 was expressed in a diffuse pattern in most tumor subtypes, except in squamous cell carcinomas, where it appeared in a focal pattern in 50% of specimens. Thus, Msi1 is a sensitive and specific diagnostic marker for all lung cancer subtypes.
| S-EPMC3742834 | biostudies-other
Project description:NANOG has been demonstrated to play an essential role in the maintenance of embryonic stem cells, and its pseudogene, NANOGP8, is suggested to promote the cancer stem cell phenotype. As the roles of these genes are intimately involved with glioblastoma multiforme progression and exosomes are critical in intercellular communication, we conducted a detailed analysis of the association of the NANOG gene family with exosomes to identify diagnostic markers for cancer. Exosomes were precipitated from conditioned culture media from various cell lines, and NANOG gene fragments were directly amplified without DNA isolation using multiple primer sets. The use of the enzymes AlwNI and SmaI with restriction fragment length polymorphism analysis functioned to distinguish NANOGP8 from other NANOG family members. Collectively, results suggest that the NANOG DNA associated with exosomes is not full length and that mixed populations of the NANOG gene family exist. Furthermore, sequence analysis of exosomal DNA amplified with a NANOGP8 specific primer set frequently showed an insertion of a 22 bp sequence into the 3' UTR. The occurrence rate of this insertion was significantly higher in exosomal DNA clones from cancer cells as compared to normal cells. We have detected mixed populations of NANOG DNA associated with exosomes and have identified preferential modulations in the sequences from cancer samples. Our findings, coupled with the properties of exosomes, may allow for the detection of traditionally inaccessible cancers (i.e. GBM) through minimally invasive techniques. Further analysis of exosomal DNA sequences of NANOG and other embryonic stemness genes (OCT3/4, SOX2, etc.) may establish a robust collection of exosome based diagnostic markers, and further elucidate the mechanisms of cancer formation, progression, and metastasis.
| S-EPMC5963750 | biostudies-literature
Project description:BackgroundAlthough circular RNAs (circRNAs) have recently garnered interest as disease markers, they have been relatively poorly studied as a biomarker in colorectal cancer (CRC). In this study, we aimed to screen the exosome-derived circRNAs in CRC and explore their potential as diagnostic and prognostic biomarkers of CRC METHODS: Exosomes were extracted from the plasma using a kit and validated by immunoblotting, transmission electron microscopy, and particle size analysis. The microarray datasets were employed to identify differentially-expressed circRNAs from plasma exosomes. Real-time quantitative reverse transcription PCR (RT-qPCR) verified the results of the microarray analysis, and Receiver operating characteristic (ROC) curve revealed the diagnostic ability of a single circRNA. The Starbase combined with microT, miRmap, and RNA22 were used to establish a circRNA-miRNA-mRNA network. Gene ontology, Kyoto Encyclopedia of Genes, Genomes pathway enrichment analysis, and Gene Set Enrichment Analysis were applied to determine potential functions of the identified mRNAs RESULTS: Comparing the microarray of plasma exosome-derived circRNAs and the microarray downloaded from the GEO database, 15 candidate circRNAs with up-regulated expression were identified. RT-qPCR verified that hsa_circ_0003270 (circGAPVD1) was upregulated in CRC plasma exosomes. ROC analysis showed that circGAPVD1 in plasma exosomes has potential diagnostic value for CRC. The sensitivity and specificity of circGAPVD1 in the diagnosis of CRC were found to be 75.64 and 71.79%, respectively (area under ROC = 0.7662). Furthermore, the lymph node metastasis and TNM staging of patients were positively correlated with high expression of circGAPVD1. Combined with the ENCORI database and GEO datasets, we identified the circGAPVD1-related ceRNA network. The enrichment analysis revealed that key nodes in the ceRNA network participate in many important signaling pathways such as protein post-translational modifications CONCLUSION: Our results revealed the diagnostic efficiency of circGAPVD1 in plasma exosomes. The highly expressed circGAPVD1 is expected to be a novel diagnostic marker for CRC.
| S-EPMC10034150 | biostudies-literature
Project description:ObjectiveElevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways.MethodsIn a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach.ResultsSubjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites).ConclusionsOur data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.
| S-EPMC5220278 | biostudies-literature
Project description:Pancreatic cancer has a dismal prognosis partly due to late diagnosis, where a reliable non-invasive diagnosis is urgently wanted. We here explored, whether serum-derived PaCa exosomes may provide a diagnostic means and microRNA may be advantageous. Exosomes were collected from the serum of 133 patients with pancreatic cancer, 22 patients with non-malignant pancreatic tumors, 25 patients with chronic pancreatitis and 20 healthy donors. Exosomes were isolated by ultracentrifugation and used qRT-PCR for miRNA quantification and miRCURY LNA microRNA Array for miRNA analysis.
2014-12-01 | GSE50632 | GEO