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Single-cell analysis reveals subtypes of colorectal tumours

Wed, 04/26/2017 - 14:44
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Single-cell analysis reveals subtypes of colorectal tumours

Advances in tumour genomic sequencing have improved classification of tumour subtypes, guiding more precise cancer treatments and improving patient survival. However, tumours typically contain a variety of cancerous and noncancerous cells that all contribute to the biology of the tumour. By combining single-cell genomics and computational techniques, a research team has defined cell-type composition of cancerous cells from 11 colorectal tumours, as well as adjacent noncancerous cells, a key to more targeted diagnosis and treatment. 

"Using single-cell signatures, colorectal cancers can be further divided into subgroups based on cell-type composition of tumours,” said The Jackson Laboratory (JAX) research scientist, Dr Elise Courtois, co-first author of a study published in Nature Genetics. “Because each of these subgroups has a different survival probability, our approach can provide oncologists with better information about prognosis and treatment options."

To date, gene expression in such tumours has been profiled using bulk transcriptome methods, providing a single transcriptome measure for what, in essence, represents many cell types. By employing single-cell transcriptomic technology it is now possible to deconstruct a tumour into its component cell-type parts and therefore gain a better understanding of the underlying biology.

Robson and co-senior authors Shyam Prabhakar, a computational biologist at the Genome Institute of Singapore, and Iain Beehuat Tan, a medical oncologist at the National Cancer Centre Singapore, led an effort that screened 626 randomly selected individual cells from the colorectal tumours and adjacent normal cell samples using single-cell RNA sequencing.

Computationally examining each cell's transcriptome (the readout of all the messenger RNA molecules in that cell) using their new algorithm, the researchers identified two distinct subtypes of cancer-associated fibroblasts (CAFs). These CAFs significantly contributed to the mesenchymal gene expression found in bulk tumour transcriptome data, a signature more often associated with a cancer cell process known as epithelial-mesenchymal transition. Their data make the case that CAFs contribute to a worse prognosis in colorectal cancer patients.

These findings, Robson notes, show promise for even more refined classification of colorectal and other tumours in the future. "And as the cost of single-cell transcriptomic analysis continues to drop, oncologists can access better tumour profiling to guide the treatment of cancer patients," he says.

The researcher paper, ‘{{Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors}}’, was published in the journal, Nature Genetics.

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