I have two groups of patients : Responders to chemotherapy and non-responders to chemotherapy. I treat this as a dichotomous outcome we can call response to chemotherapy.

For a fixed set of cancer driver genes, I have calculated cancer cell fraction (ccf) for each group.

Does anyone know of any interaction or relation of response to chemotherapy and ccf?

  • $\begingroup$ Can you clarify how cancer cell fraction is derived from what you call "cancer driver genes"? I understand ccf to be the proportion of cancer cells among all cells, which is not directly related to driver genes. Are you estimating ccf somehow from driver gene copy number or allele frequency or something? That might lead to a different interpretation of ccf than other ways of estimating it. Can you link to a method or other tool? I found one possible method but I assume there are many others: nature.com/articles/s41467-020-14351-8 $\endgroup$ – Maximilian Press Apr 3 '20 at 17:44
  • $\begingroup$ I have estimated ccf from variant allele frequency $\endgroup$ – Angel Apr 3 '20 at 19:43

Assuming that my comment is trivial, I think that there is some literature on this question. I'm assuming that the ccf in question is for the relevant tissue type for the cancer.

You might also consider cross-posting to SE Medical Sciences, where people are more familiar with these subjects.

Of course, naively one would expect that a larger ccf would yield a larger possible population of cancer cells to provide "escape" mutations or resistance to chemo, so high ccf should then be negatively predictive. As an extreme example, a highly metastatic cancer will have a high ccf over the whole body, and will be more resistant to chemo just because that's a highly advanced disease.

However, as usual things are a little more complex. The ccf itself has subpopulations. The following I got by just googling around a little bit. For some of the fundamental thinking on this, see this old paper. In this paper, the author puts emphasis for example on the fraction of cancer cells in each stage of the cell cycle; this results in what the author calls "clonogenic" and "nonclonogenic" populations that respectively yield new clones of cancer cells or do not yield new clones. Probably that terminology is somewhat outdated, but it gives a sense of the problem; related are "tumor stem cells". For a more modern treatment, you can look at this.

For a med school lecture treatment, see here to learn a little bit more. For an example of a recent prediction study which uses omic data to predict chemo response, which might be helpful in reformulating your study, see here.

In other words, not all tumor cells are created equal, some are more likely to resist chemo than others. However, overall I would expect that there is probably some kind of relationship between ccf and response to chemo, because they are both related to the mediator variable "number of clonogenic cancer cells"; it's just a somewhat oversimplified model compared to the actual biology, so it looks like the publications in question don't tend to focus on it.


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