Fig. 6: A YC-defined gene signature marks radiotherapy response.
a, Venn diagram of the pan-cancer trajectory genes (described in Extended Data Fig. 1d), radiosensitivity trajectory genes (described in Extended Data Fig. 3f) and irradiation-affected trajectory genes (described in Extended Data Fig. 4b). The 147 genes forming the intersection of the latter two groups are termed the radiotherapy responsiveness signature genes (Venn diagram generated with Meta-Chart software). b, Intersection of MSigDB pathway enrichment ontology analysis of the three trajectory gene sets detailed in a. Dotted line shows 0.05 FDR threshold. c, UCSC Genome Browser view of an irradiation-responsive dual promoter, GMPR2 (guanosine monophosphate reductase 2), highlighting the location of the annealing sites for primers designed to segregate the expression of the YC and YR components through RT–qPCR analysis. Direction of transcription (on the reverse strand) is illustrated by arrows. d, Bar graphs showing the relative expression of the YC and YR components of five candidate dual-initiation genes in the CRC organoids and upon irradiation, calculated by RT–qPCR analysis. (n = 2 responsive, n = 1 moderately responsive and n = 2 non-responsive organoids; *P < 0.05, two-tailed unpaired t-test, statistically analyzed comparisons were responsive versus non-responsive and control versus irradiated; data are presented as mean values ± s.e.m., full list of P values available in the Source data). e, Bar graphs showing the relative expression of the YC and YR components of five candidate dual-initiation genes in 12 CRC clinical samples (six responsive and six non-responsive independent biological samples), calculated by RT–qPCR analysis. (P < 0.0001, 0.0001, 0.0097 and 0.0046 for C9orf85, PRORP, SND1 and GMPR2, respectively; two-tailed unpaired t-test, statistically analyzed comparisons were responsive versus non-responsive and control versus irradiated; data are presented as mean values ± s.e.m.).
