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Publication Highlight – Application of single-cell sequencing in human cancer

Application of single-cell sequencing in human cancer

Mattias Rantalainen

Briefings in Functional Genomics, Volume 17, Issue 4, July 2018, Pages 273–282, https://doi.org/10.1093/bfgp/elx036

Published: 02 November 2017

This publication provides a substantial overview of all of the steps required in single cell RNA sequencing, including information about existing technologies available to execute each step, and the many applications of single cell RNA seq in human cancer research. It also includes an interesting discussion about the very high potential and limitations currently facing single cell RNA-seq studies and human cancer research.

Single cell RNA sequencing (single cell RNA-seq) plays a particularly important role in understanding cancer and phenotyping tumors. Even within the same type of cancer, each tumor can be very different, making a precision medicine approach very important.

“The clinical importance of comprehensive molecular phenotyping of cancer tumours is increasing with the advent of precision medicine…, which aims to provide tailored treatment to individual patients based on their molecular phenotype.”

Tumors are often heterogenous even within themselves. This makes it particularly difficult to truly characterize tumors in order to  determine the best treatment plan or course of action for a particular patient.

“Intra-tumour heterogeneity is common in many cancer diseases and related to treatment response, progression and survival outcomes. Intra-tumour heterogeneity can only be fully characterized at the single-cell level.”

As with bulk-level RNA sequencing, sample collection, preparation, and preservation are key for downstream analysis of single cell RNA seq:

“Clinical samples are routinely prepared as formalin-fixed, paraffin-embedded (FFPE), which limits the opportunity for single-cell sequencing, especially in respect to RNA sequencing.“

CellCover is mentioned as a formaldehyde alternative for sample preservation with reference to another single cell RNA sequencing study  using this cell fixation product:

“Recently, a method for preservation of cells for [single cell RNA-seq] without chemical crosslinking or freezing [using CellCover (AL Anacyte Laboratories UG), DNA RNA preservation] was also applied in a [single cell RNA-seq] study.”

Many existing single cell RNA seq studies at the time of publication included a small cohort, and this publication concludes:

“The next step in application of single-cell methods in the study of human cancers is to initiate studies that include larger patient cohorts; larger numbers of single-cells and that also consider clinical outcomes.”

It is likely that single-cell molecular phenotyping may surpass bulk average molecular profiling in many cancer research and clinical applications in the future as the importance of precision medicine for treating each patient and each tumor individually becomes more and more apparent.

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