The local tumor microbiome is associated with survival in late-stage colorectal cancer patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB57580 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR10493000_1.fastq.gz | Fastqsanger.gz | |||
| ERR10493000_2.fastq.gz | Fastqsanger.gz | |||
| ERR10493100_1.fastq.gz | Fastqsanger.gz | |||
| ERR10493100_2.fastq.gz | Fastqsanger.gz | |||
| ERR10493200_1.fastq.gz | Fastqsanger.gz |
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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.
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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%
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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.
This model is hosted on
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MODEL1708310001.
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Project description:miRNA and colorectal cancer: associations with tumor phenotype and survival
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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.
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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.
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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
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