The local tumor microbiome is associated with survival in late-stage colorectal cancer patients
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ABSTRACT:
PROVIDER: PRJEB57169 | ENA |
REPOSITORIES: ENA
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Project description:Microbiome in colorectal cancer survival
| PRJEB57580 | ENA
Project description:The aim of the study was to elucidate the association between copy number alterations and gene expression profiles in colorectal cancer patients and to identify molecular signatures that are associated with survival.
2016-05-25 | E-MTAB-4353 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and is a heterogeneous disease, with differences between cancer in the right colon, left colon, and rectum. In this study, plasma samples from CRC patients with varying stage (II or III), primary tumor location (right colon, left colon, or rectum) and survival (survived or died due to CRC) were studied with quantitative label-free proteomics using ultra-definition MSE. Patients were also divided into subgroups based on preoperative radiotherapy status and gender. Further analysis subsequently identified multiple plasma proteins whose expression differed depending on tumor stage, location, patient survival, preoperative radiotherapy status, or gender.
2019-08-22 | PXD013150 | Pride
Project description:Claret2009 - Predicting phase III overall survival in colorectal cancer
This model is described in the article:
Model-based prediction of
phase III overall survival in colorectal cancer on the basis of
phase II tumor dynamics.
Claret L, Girard P, Hoff PM, Van
Cutsem E, Zuideveld KP, Jorga K, Fagerberg J, Bruno R.
J. Clin. Oncol. 2009 Sep; 27(25):
4103-4108
Abstract:
PURPOSE: We developed a drug-disease simulation model to
predict antitumor response and overall survival in phase III
studies from longitudinal tumor size data in phase II trials.
METHODS: We developed a longitudinal exposure-response
tumor-growth inhibition (TGI) model of drug effect (and
resistance) using phase II data of capecitabine (n = 34) and
historical phase III data of fluorouracil (FU; n = 252) in
colorectal cancer (CRC); and we developed a parametric survival
model that related change in tumor size and patient
characteristics to survival time using historical phase III
data (n = 245). The models were validated in simulation of
antitumor response and survival in an independent phase III
study (n = 1,000 replicates) of capecitabine versus FU in CRC.
RESULTS: The TGI model provided a good fit of longitudinal
tumor size data. A lognormal distribution best described the
survival time, and baseline tumor size and change in tumor size
from baseline at week 7 were predictors (P < .00001).
Predicted change of tumor size and survival time distributions
in the phase III study for both capecitabine and FU were
consistent with observed values, for example, 431 days (90%
prediction interval, 362 to 514 days) versus 401 days observed
for survival in the capecitabine arm. A modest survival
improvement of 39 days (90% prediction interval, -21 to 110
days) versus 35 days observed was predicted for capecitabine.
CONCLUSION: The modeling framework successfully predicted
survival in a phase III trial on the basis of capecitabine
phase II data in CRC. It is a useful tool to support
end-of-phase II decisions and design of phase III studies.
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2017-08-31 | MODEL1708310001 | BioModels
Project description:miRNA and colorectal cancer: associations with tumor phenotype and survival
| PRJNA475254 | ENA
Project description:IntroductionAlthough patients with colorectal cancer (CRC) can receive optimal treatment, the risk of recurrence remains. This study aimed to evaluate whether the tumor microbiome can be a predictor of recurrence in patients with stage III CRC.MethodsUsing 16S rRNA gene sequencing, we analyzed the microbiomes of tumor and adjacent tissues acquired during surgery in 65 patients with stage III CRC and evaluated the correlation of the tissue microbiome with CRC recurrence. Additionally, the tumor tissue microbiome data of 71 patients with stage III CRC from another center were used as a validation set.ResultsThe microbial diversity and abundance significantly differed between tumor and adjacent tissues. In particular, Streptococcus and Gemella were more abundant in tumor tissue samples than in adjacent tissue samples. The microbial diversity and abundance in tumor and adjacent tissues did not differ according to the presence of recurrence, except for one genus in the validation set. Logistic regression analysis revealed that a recurrence prediction model including tumor tissue microbiome data had a better prediction performance than clinical factors (area under the curve [AUC] 0.846 vs. 0.679, p = 0.009), regardless of sex (male patients: AUC 0.943 vs. 0.818, p = 0.043; female patients: AUC 0.885 vs. 0.590, p = 0.017). When this prediction model was applied to the validation set, it had a higher AUC value than clinical factors in female patients.ConclusionOur results suggest that the tumor microbiome of patients with CRC be a potential predictor of postoperative disease recurrence.
| S-EPMC10641399 | biostudies-literature
Project description:Colorectal cancer (CRC) is the fourth leading cause of cancer-related death worldwide due to high apoptotic resistance and metastatic potential. Since mutations as well as deregulation of CK1 isoforms contribute to tumor development and progression, CK1 has become an interesting drug target. In this study, we show that CK1 isoforms are differently expressed in colon tumor cell lines and that growth of these cell lines can be inhibited by CK1-specific inhibitors. Furthermore, expression of CK1δ and ε is changed in colorectal tumors and high CK1ε expression levels significantly correlate with prolonged patients' survival. In addition to changes in CK1δ and ε expression, mutations within exon 3 of CK1δ were detected in colorectal tumors. These mutations influence ATP binding, leading to changes in the kinetic parameters. Overexpression of these mutants in HT29 cells alters their ability to grow anchorage independently. Consistent with these results, these CK1δ mutants lead to differences in proliferation rate and tumor size in xenografts due to changes in gene expression, especially in genes involved in regulation of cell proliferation, cell cycle, and apoptosis. In summary, our results provide evidence that changes in the expression levels of CK1 isoforms in colorectal tumors correlate with the survival of patients and that CK1δ mutations affect growth and proliferation of tumor cells and induced tumor growth in xenografts, leading to the assumption that CK1 isoforms provide interesting targets in new colorectal cancer therapy concepts.
2017-05-19 | GSE57840 | GEO
Project description:Surgical resection is the major clinical intervention for Stage III colorectal cancer (CRC) currently. However, as much as 30.8% of the patients who had ever taken curative resection came out of recurrence eventually. Therefore, to facilitate formulating effective treatment plans, there is an intense demand for Stage III CRC post-surgical prognostic biomarkers. In this study, we identified total 146 differentially expressed proteins (DEPs) associated with poor prognosis in Stage III CRC patients with TMT-based quantitative mass spectrometry (MS). In these DEPs, the protein expression level of R-Ras and Transgelin were tested with immunohistochemistry (IHC) of 192 individual specimens. Further Kaplan-Meier analysis revealed that the level of R-Ras and Transgelin is associated with patients’ 5-year overall survival (OS) and disease-free survival (DFS) significantly, and multivariate Cox-regression analyses revealed that R-Ras and Transgelin are independent prognostic factors for OS and DFS respectively. In conclusion, our study presents that R-Ras and Transgelin are potential post-surgical prognostic biomarkers of Stage III CRC.
2016-06-20 | PXD002903 | Pride
Project description:MicroRNAs (miRNA) are a class of small regulatory RNAs that mediate post-transcriptional silencing of specific target mRNAs. Data suggest the importance of miRNAs to cancer development and possibly to survival. Our overall hypothesis is that miRNA expression is unique to tumor molecular phenotype; that miRNA expression levels at time of diagnosis predicts survival; and that miRNA expression is associated with inflammation-related genetic and lifestyle factors key to colorectal cancer (CRC). This study takes a two pronged approach to addressing our hypotheses. While we propose to validate previously identified miRNAs that have been identified as associated with CRC (either by differential expression or from assessment of mutations), we will add to the field through discovery of new and important associations that may be unique to specific molecular phenotypes, to polyp to cancer progression, and to survival. We have analyzed the expression of 2006 human miRNAs using data derived from tumor and paired normal tissue at time of diagnosis from: 1975 people with incident colon cancer or rectal cancer and 290 polyps from colon and rectal cases (included in this study) who reported a prior polyp. MiRNA was obtained from dissected paraffin-embedded tissue and assessed using an Agilent microarray platform. We intend to extend our validation of previously identified mutated miRNAs and differentially expressed miRNAs to determine if these alterations are associated with specific tumor molecular phenotype (TP53, KRAS2, CIMP+, and for colon tumors MSI+), inflammation-related factors, clinical factors and survival. We will identify associations with miRNAs that are related to specific molecular phenotypes, with drivers in the carcinogenic process, and with clinical features and survival. These miRNAs will be validated using targeted Agilent Platform. Associations will be tested based on differential expression for both individual and groups of miRNAs using recent extensions of several statistical methods including ANOVA, logistic regression, and Cox proportional hazards models. Our sample size allows for both a training and validation component, and provides sufficient statistical power to meet the study goals. MiRNAs that are differentially expressed in polyps and in subsequent tumors will provide new insights into targets for screening and treatment as well as provide support that miRNAs function as the “driver” in the carcinogenic process. Testing of mutated miRNAs identified from sequencing in conjunction with tumor phenotype, clinical, and survival data will further validate the importance of these miRNAs, and provide insight as to which CRC molecular pathway the miRNAs function. Our rich dataset of lifestyle, genetic, clinical and prognosis, and tumor molecular phenotype on 1975 CRC and paired normal tissue allows us to examine factors that are associated with miRNA expression and mutation in a large sample of population-based cases in the most cost-efficient manner possible. The miRNAs identified in these analyses will elucidate pathways important in the etiology of CRC and will provide insight into potential targets for screening and treatment. MiRNAs are small, non-protein-coding RNA molecules that regulate gene expression either by post-transcriptionally suppressing mRNA translation or by mRNA degradation. We examine differentially expressed miRNAs in colorectal carcinomas, adenomas, and normal colonic mucosa. Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma/normal paired samples and 290 adenoma tissue samples were run on the Agilent Human miRNA Microarray V19.0 which contained 2006 miRNAs. We tested for significant differences in miRNA expression between paired carcinoma/adenoma/normal colonic tissue samples. Fewer than 600 miRNAs were expressed in >80% of people for colonic tissue; of these 86.5% were statistically differentially expressed between carcinoma and normal colonic mucosa using a False Discovery Rate of 0.05. Roughly half of these differentially expressed miRNAs showed a progression in levels of expression from normal to adenoma to carcinoma tissue. Other miRNAs appeared to be altered at the normal to adenoma stage, while others were only altered at the adenoma to carcinoma stage or only at the normal to carcinoma stage. Evaluation of the Agilent platform showed a high degree of repeatability (r=0.98) and reasonable agreement with the NanoString platform. Our data suggest that miRNAs are highly dysregulated in colorectal tissue among individuals with colorectal cancer; the pattern of disruption varies by miRNA as tissue progresses from normal to adenoma to carcinoma.
2018-06-09 | GSE115513 | GEO
Project description:Colorectal cancer (CRC) has one of the highest worldwide incidences and mortality rates. Compared to surgery alone, adjuvant 5-Fluorouracil (5FU)-based chemotherapy improves 5-year overall survival (OS) in only 3-4% of stage II and 15-20% of stage III patients in unselected populations. Significant advances have been made in the molecular stratification of CRC, with the emerging Consensus Molecular Subtype (CMS) and Colorectal Cancer Intrinsic Signature (CRIS) transcriptomics-based classification systems; however, the therapeutic impact of molecular stratification has so far been limited. In an effort to identify subgroups of patients benefitting from chemotherapy, we assessed which CMS and CRIS subgroups of stage II and III CRC benefitted from adjuvant 5FU-based chemotherapy using in-house and published datasets.
2017-12-31 | GSE103479 | GEO