Dataset Information

High levels of cleaved caspase-3 in colorectal tumour stroma predict good survival.

ABSTRACT:

Aim

The primary aim was to determine the prognostic significance of apoptosis in colorectal tumour cells and tumour-associated stroma. A secondary aim was to determine whether apoptosis was related to immune surveillance.

Methods

Immunohistochemistry was performed using monoclonal antibodies recognising cleaved caspase-3 (CC3), cleaved poly (ADP-ribose) polymerase (PARP), p53, Bcl2, MHC-II, B cells (CD16), macrophages (CD68) and T cells (CD3), on a tissue microarray of 462 colorectal tumours.

Results

Kaplan-Meier analysis demonstrated that patients with high expression of CC3 in the tumour or CC3 or cleaved PARP in tumour-associated stroma have a good prognosis. This suggests that tumour stroma is promoting tumourigenesis and that high levels of death within the stroma breaks this link. CC3 levels in the tumour correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. CC3 levels on tumour-associated stroma also correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. Tumour cells express MHC-II in response to IFN-?, suggesting that this may be one of the initiators of apoptosis within the good prognosis tumours. Although 73% of the MHC-II-positive tumour had high levels of apoptosis, many tumours had high levels of apoptosis in the absence of MHC-II, implying that this is only one of many causes of apoptosis within tumours. On multivariate analysis, using Cox's proportional hazards model, tumour stage, vascular invasion and expression of CC3 in tumour-associated stroma were shown to be independent markers of prognosis.

Conclusion

This study shows that a high level of apoptosis within colorectal tumour-associated stroma is an independent marker of good prognosis.

SUBMITTER: Noble P

PROVIDER: S-EPMC3670501 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Publications

High levels of cleaved caspase-3 in colorectal tumour stroma predict good survival.

Noble P P Vyas M M Al-Attar A A Durrant S S Scholefield J J Durrant L L

British journal of cancer 20130416 10

<h4>Aim</h4>The primary aim was to determine the prognostic significance of apoptosis in colorectal tumour cells and tumour-associated stroma. A secondary aim was to determine whether apoptosis was related to immune surveillance.<h4>Methods</h4>Immunohistochemistry was performed using monoclonal antibodies recognising cleaved caspase-3 (CC3), cleaved poly (ADP-ribose) polymerase (PARP), p53, Bcl2, MHC-II, B cells (CD16), macrophages (CD68) and T cells (CD3), on a tissue microarray of 462 colorec ...[more]

PMID: 23591201

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Project description:Background and aimsThe gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.MethodsA multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.ResultsThirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10-11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR = 1.30 × 10-12), but metabolite clusters were not associated with disease-free survival (p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency (p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7.ConclusionsNetworks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection. Video Abstract.

Dataset Information

High levels of cleaved caspase-3 in colorectal tumour stroma predict good survival.

Aim

Methods

Results

Conclusion

Publications

High levels of cleaved caspase-3 in colorectal tumour stroma predict good survival.

Similar Datasets

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