The novel diagnostic method of colorectal cancer by methyl mercaptan
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ABSTRACT:
DISEASE(S): The Novel Diagnostic Method For Colorectal Cancer: Detection Of Methyl-mercaptan From Flatus
PROVIDER: 2643463 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:BackgroundTo improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer.Methodology/principal findingsWe performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS). First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD% values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night) and inter-day (among 3 days) variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N?=?60; N?=?12 for each stage from 0 to 4) and age- and sex-matched healthy volunteers (N?=?60) as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0%, 85.0%, and 85.0%, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0%, 96.7%, and 65.8%, respectively, and those of CA19-9 were 16.7%, 100%, and 58.3%, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N?=?59) and healthy volunteers (N?=?63) as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1%, 81.0%, and 82.0%, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0-2 colorectal cancer (82.8%).Conclusions/significanceOur prediction model established via GC/MS-based serum metabolomic analysis is valuable for early detection of colorectal cancer and has the potential to become a novel screening test for colorectal cancer.
| S-EPMC3394708 | biostudies-literature
Project description:Global microRNA expression profiling of serum were collected using Agilent miRNA microarrays (G4471A Human, Amadid 29297, Sanger 14) carrying 887 individual human miRNA probes. Two different sources of RNA were analyzed: serum from NMRI-nu/nu mice carrying a xenograft tumor derived from human primary pancreatic ductal adenocarcinomas (CA, n=6) and serum from tumor free control NMRI-nu/nu mice (N, n=6) Two condition (CA, N), each condition is represented by 6 biological replicates
2013-07-01 | E-GEOD-34052 | biostudies-arrayexpress
Project description:ObjectiveThe follow-up of the increasing number of cancer survivors threatens to overload the health care system. While short message system (SMS)-based communication is widely used in other areas of the health care system, there are no studies of its appliance in cancer surveillance. The aim of the current study was to analyze the acceptability, convenience and impact of a novel mobile phone messaging -based system (Mobile-CEA) on health personnel contacts in patients with colorectal cancer (CRC) during 2 years of follow-up.MethodsThe follow-up data of 52 curatively treated patients with CRC (22 Mobile-CEA-, 30 standard surveillance) was collected retrospectively from the electronic archives. Mobile-CEA patient satisfaction was measured by a tailored non-validated questionnaire. Health personnel satisfaction was assessed by personal interviews.ResultsMobile-CEA surveillance group had less health personnel contacts than the standard surveillance group: median 3 (min 0-max 7) vs 5 (min 4-max 7) and 77.2% of the Mobile-CEA group had less than 4 contacts (minimum with the standard surveillance) to health personnel. There were no recurrences in either group. Mobile-CEA patients were satisfied with this novel follow-up method. Health personnel considered it as a practical and safe tool in CRC surveillance.ConclusionMobile-CEA surveillance seems to be a promising and effective follow-up method for curatively treated patients with CRC. Further studies and experiences are needed.
| S-EPMC9209784 | biostudies-literature
Project description:Background and aimAberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC). The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort.Patients and methodsMethylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients.ResultsMethylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001); however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7%) and IGFBP3 (83%) in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%). Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR?=?0.49, 95% CI: 0.28-0.85, p?=?0.01). Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy.ConclusionBy analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients.
| S-EPMC4134211 | biostudies-literature
Project description:Objective Mesothelin is a cell surface protein and overexpressed in many cancers. However, the potential value of mesothelin as plasma biomarker in colorectal cancer has not been explored. The purpose of this study was to identify whether plasma mesothelin is a suitable diagnostic and prognostic biomarker for colorectal cancer. Methods We performed a two-stage case-control study to evaluate plasma mesothelin levels in colorectal cancer using enzyme-linked immunosorbent assay (ELISA). Preoperative and postoperative plasma were collected to examine the level changes influenced by surgery. Receiver operating characteristic (ROC) curves were applied to identify the diagnostic value of plasma mesothelin. We also conducted univariate Kaplan-Meier survival analysis and Cox regression analysis of patients with survival information. Results We found that the plasma mesothelin levels in colorectal cancer patients were significantly higher than that in the controls (P < 0.001) with an AUC value of 0.690 (95% CI = 0.625 to 0.752). Individuals with lower mesothelin level had a longer survival time (adjusted HR = 4.43, 95% CI = 1.93-10.15, P < 0.001). Furthermore, Patients had slightly decreased mesothelin levels in postoperative plasma than preoperative plasma, although the alteration was not statistically significant (P = 0.052). Conclusion Our findings highlight the correlative relationship between plasma mesothelin levels and the presence and progression of colorectal cancer. Plasma mesothelin may be a potential diagnostic and, or prognostic biomarker for colorectal cancer.
| S-EPMC5479240 | biostudies-literature
Project description:Global microRNA expression profiling of serum were collected using Agilent miRNA microarrays (G4471A Human, Amadid 29297, Sanger 14) carrying 887 individual human miRNA probes. Two different sources of RNA were analyzed: serum from NMRI-nu/nu mice carrying a xenograft tumor derived from human primary pancreatic ductal adenocarcinomas (CA, n=6) and serum from tumor free control NMRI-nu/nu mice (N, n=6)
2013-07-01 | GSE34052 | GEO
Project description:BackgroundKRAS, BRAF and PIK3CA mutations are frequently observed in colorectal cancer (CRC). In particular, KRAS mutations are strong predictors for clinical outcomes of EGFR-targeted treatments such as cetuximab and panitumumab in metastatic colorectal cancer (mCRC). For mutation analysis, the current methods are time-consuming, and not readily available to all oncologists and pathologists. We have developed a novel, simple, sensitive and fully automated molecular diagnostic system (AMDS) for point of care testing (POCT). Here we report the results of a comparison study between AMDS and direct sequencing (DS) in the detection of KRAS, BRAF and PI3KCA somatic mutations.Methodology/principal findingDNA was extracted from a slice of either frozen (n?=?89) or formalin-fixed and paraffin-embedded (FFPE) CRC tissue (n?=?70), and then used for mutation analysis by AMDS and DS. All mutations (n?=?41 among frozen and 27 among FFPE samples) detected by DS were also successfully (100%) detected by the AMDS. However, 8 frozen and 6 FFPE samples detected as wild-type in the DS analysis were shown as mutants in the AMDS analysis. By cloning-sequencing assays, these discordant samples were confirmed as true mutants. One sample had simultaneous "hot spot" mutations of KRAS and PIK3CA, and cloning assay comfirmed that E542K and E545K were not on the same allele. Genotyping call rates for DS were 100.0% (89/89) and 74.3% (52/70) in frozen and FFPE samples, respectively, for the first attempt; whereas that of AMDS was 100.0% for both sample sets. For automated DNA extraction and mutation detection by AMDS, frozen tissues (n?=?41) were successfully detected all mutations within 70 minutes.Conclusions/significanceAMDS has superior sensitivity and accuracy over DS, and is much easier to execute than conventional labor intensive manual mutation analysis. AMDS has great potential for POCT equipment for mutation analysis.
| S-EPMC3650034 | biostudies-literature
Project description:Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. Current methods for CRC screening commonly consist of a combination of faecal immunochemical test (FIT) for stool occult blood detection and invasive procedures such as colonoscopy. Considering the slow progression of CRC, and that symptoms usually emerge at advanced stages, its early diagnostic can limit cancer's spread and provide a successful treatment. Biomarkers have a high potential for the diagnosis of CRC in either blood or stool samples. In this study, we analysed the diagnostic value of six different biomarkers in stool samples of patients with CRC, advanced adenomas, other lesions and healthy individuals. We have also assessed the overall performance of the combination of these biomarkers for CRC detection. The results indicate that haemoglobin (Hb) and M2-pyruvate kinase (M2-PK) levels were increased in CRC patients in comparison to the controls. Conversely, the concentrations of matrix metalloproteinase (MMP)-2, MMP-9, and tumour necrosis factor-alpha (TNF-α) were not significantly different between the tested groups. The combination of FIT-Hb with the M2-PK levels increased the specificity or sensitivity for CRC detection and thus present potential as faecal diagnostic biomarkers for CRC.
| S-EPMC8582677 | biostudies-literature
Project description:Background: Multi-omics analyses are profitable for discovering novel biomarkers and drug targets, but such integrated examinations on mitochondria of colorectal cancer (CRC) patients are lacking. Methods: We investigated global structural variants, DNA methylation, chromatin accessibility, proteome, and phosphoproteome on human CRC (n = 6-8). The alterations of mitochondria on these levels and potential upstream regulatory genes were described. Furthermore, combining with the mRNA datasets of 538 CRC and 91 colitis patients from the public databases, we identified independent prognostic factors (IPFs). Findings: Revealed by the proteogenomic analyses in our study, mitochondria altered the most among all organelles in CRC, which were also associated with patient prognosis the most. We found that the mRNA of one nuclear-coding mitochondrial gene (NCMG), HIGD1A, decreased in colitis, two subtypes of adenoma, and six subtypes of CRC, subsequently was identified as a favorable IPF for CRC. Besides, the comprehensive analyses of mitochondria by multi-omics uncovered unique proteogenomic alterations on six survival-related NCMGs. Key transcriptional factors potentially regulating the mitochondria were also unveiled, such as GLIS1, JUN, CREB1, and YAP1. Finally, p38 was highlighted as one possible central kinase involving in the modulation of mitochondrial activity in CRC patients. Interpretation: Our study presents a multilayer and molecular picture of mitochondria of CRC patients, recognizes HIGD1A as a potential prognostic biomarker, and provides new candidate genes as therapeutic targets.
2021-09-09 | PXD021314 | Pride
Project description:Background: Multi-omics analyses are profitable for discovering novel biomarkers and drug targets, but such integrated examinations on mitochondria of colorectal cancer (CRC) patients are lacking. Methods: We investigated global structural variants, DNA methylation, chromatin accessibility, proteome, and phosphoproteome on human CRC (n = 6-8). The alterations of mitochondria on these levels and potential upstream regulatory genes were described. Furthermore, combining with the mRNA datasets of 538 CRC and 91 colitis patients from the public databases, we identified independent prognostic factors (IPFs). Findings: Revealed by the proteogenomic analyses in our study, mitochondria altered the most among all organelles in CRC, which were also associated with patient prognosis the most. We found that the mRNA of one nuclear-coding mitochondrial gene (NCMG), HIGD1A, decreased in colitis, two subtypes of adenoma, and six subtypes of CRC, subsequently was identified as a favorable IPF for CRC. Besides, the comprehensive analyses of mitochondria by multi-omics uncovered unique proteogenomic alterations on six survival-related NCMGs. Key transcriptional factors potentially regulating the mitochondria were also unveiled, such as GLIS1, JUN, CREB1, and YAP1. Finally, p38 was highlighted as one possible central kinase involving in the modulation of mitochondrial activity in CRC patients. Interpretation: Our study presents a multilayer and molecular picture of mitochondria of CRC patients, recognizes HIGD1A as a potential prognostic biomarker, and provides new candidate genes as therapeutic targets
2021-09-09 | PXD021318 | Pride