Unknown,Transcriptomics,Genomics,Proteomics

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Expression profiling of budding cells in colorectal cancer suggests an EMT-like phenotype and molecular subtype switching

ABSTRACT: Tumour buds undergo phenotype switching while detaching from the main tumour, as they acquire more migratory characteristics and tend to stop proliferating. Simultaneously, an EMT-like signature is observed in the tumour buds under the form of active WNT, TGF and receptor tyrosine kinase signalling. In addition, FOXA2 and RUNX2 well known transcription factors in other cancer types were also differentially expressed in the buds compared to the main tumour mass, hinting at the potential role in tumour budding and initiation of metastasis in colorectal cancer.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Bram Boeckx

PROVIDER: E-MTAB-4065 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. Some of these patients may become long-term survivors. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression to trastuzumab. 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Sixty-five per cent of tumours were poorly differentiated ductal carcinomas and hormonal receptors were present in 47%. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median progression-free survival was 10.6 years after the diagnosis of metastatic disease. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival . Gene ontology analysis demonstrated that genes involved in HIF activation, EGF receptor signalling pathway, PI3 kinase pathway, apoptosis signalling pathway and p53 pathway significantly correlated with response. The PI3K pathway was the most strongly associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. These findings support that trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression to trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy. 53 FFPE samples, which passed the RNA quality control criteria, were analyzed (45 primary tumours and 8 metastases). Among these 53 samples, 35 samples corresponded to long-term responders and 18 to the control group.

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Expression profiling of budding cells in colorectal cancer suggests an EMT-like phenotype and molecular subtype switching

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