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Colorectal Adenomas and Consensus Molecular Subtyping

ABSTRACT: Colorectal Adenomas and Consensus Molecular Subtyping

PROVIDER: PRJNA423096 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6392090_1.fastq.gz	Fastqsanger.gz
	SRR6392090_2.fastq.gz	Fastqsanger.gz
	SRR6392091_1.fastq.gz	Fastqsanger.gz
	SRR6392091_2.fastq.gz	Fastqsanger.gz
	SRR6392092_1.fastq.gz	Fastqsanger.gz

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Project description:Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas although these lesions have been associated with a significant cancer risk- twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better assess the pathogenesis of TSA. We performed a global quantitative expression profile of 44 colorectal adenomas (12 TSA, 15 CAD, 17 SSA/Ps) and 17 normal colonic mucosa, conserved as formalin-fixed paraffin-embedded samples, by the label-free quantification (LFQ) method. Unsupervised consensus hierarchical clustering applied to the whole proteomic profile of the 44 colorectal adenomas identified four subtypes. The C1 and C2 were well-individualized clusters composed of most of the CAD (14/15) and most of the SSA (13/17) respectively. This is consistent with the fact that CAD and SSA/Ps are homogeneous but distinct colorectal adenoma entities. In contrast, TSA were subdivided into C3 and C4 clusters that also contained CAD and SSA/Ps, consistent with the more heterogeneous entity of TSA at the morphological and molecular levels. The comparison of the proteome expression profile between the adenoma subtypes and normal colonic mucosa further confirmed the heterogeneous nature of TSA that merged either on CAD or SSA, while CAD and TSA formed homogeneous and distinct entities. Furthermore, we identified LEFTY1 a new potential marker for TSA that may be relevant for the TSA pathogenesis. LEFTY1 is an inhibitor of the Nodal/TGFb pathway that we found to be one of the most overexpressed proteins specifically in the TSA and confirmed by immunohistochemistry. Taken together, our study confirms that CAD and SSA form homogenous but distinct colorectal adenoma entities while TSA are an heterogeneous entity and may arise from either SSA or from normal mucosa that will evolve along the conventional adenoma pathway.

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Colorectal Adenomas and Consensus Molecular Subtyping

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