Between-tumor and within-tumor heterogeneity in invasive potential
(A) Between-tumor tests of tumor means (points) do not yield significance for a linear model (dashed line). (B) The within-tumor test shows a highly significant association (p = 2.3 × 10−45) for a linear model (dashed line) between invasiveness and total Keratin 14 protein expression for individual organoids corrected for their tumor-specific baselines. Organoids in the extreme tails are shown for symmetric tails of 10% through 50%, with organoids in the 10% tail also belonging to larger tails and so on. The dashed regression line uses all the observations (50% tails). (C) Tests performed using organoids restricted to extreme tails are also highly significant (solid line). Pooled tests of mean values for organoids in the upper vs. lower tail, performed as a paired-sample t-test for each tumor, retain sufficient power for a gene-based test at 0.05 family-wise error rate, p < 2.5 × 10−6 when correcting for 20,000 genes or proteins tested, compatible for use with RNA-Seq (dashed line).