The local tumor microbiome is associated with survival in late-stage colorectal cancer patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB57169 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Microbiome in colorectal cancer survival
| PRJEB57580 | ENA
Project description:The gut microbiome is associated with survival in colorectal cancer. Single organisms have been identified as markers of poor prognosis. However, in situ imaging of tumors demonstrate a polymicrobial tumor-associated community. To understand the role of these polymicrobial communities in survival, we conducted a nested case-control study in late-stage cancer patients undergoing resection for primary adenocarcinoma. The microbiome of paired tumor and adjacent normal tissue samples was profiled using 16S rRNA sequencing. We found a consistent difference in the microbiome between paired tumor and adjacent tissue, despite strong individual microbial identities. Furthermore, a larger difference between normal and tumor tissue was associated with prognosis: patients with shorter survival had a larger difference between normal and tumor tissue. Within the tumor tissue, we identified a 39-member community statistic associated with survival; for every log2-fold increase in this value, an individual's odds of survival increased by 20% (odds ratio survival 1.20; 95% confidence interval = 1.04 to 1.33). Our results suggest that a polymicrobial tumor-specific microbiome is associated with survival in late-stage colorectal cancer patients. IMPORTANCE Microbiome studies in colorectal cancer (CRC) have primarily focused on the role of single organisms in cancer progression. Recent work has identified specific organisms throughout the intestinal tract, which may affect survival; however, the results are inconsistent. We found differences between the tumor microbiome and the microbiome of the rest of the intestine in patients, and the magnitude of this difference was associated with survival, or, the more like a healthy gut a tumor looked, the better a patient's prognosis. Our results suggest that future microbiome-based interventions to affect survival in CRC will need to target the tumor community.
| S-EPMC10269740 | biostudies-literature
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.
This model is hosted on
BioModels Database
and identified by:
MODEL1708310001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
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:ImportanceThe gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.ObjectiveTo characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.Design, setting, and participantsThis single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021.Main outcomes and measuresFecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups.ResultsA total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy.Conclusions and relevanceThe findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.
| S-EPMC10469295 | biostudies-literature
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