Figure 4.

Effects of Chemoradiotherapy (CRT) on Tumors in Cervical Cancer Patients. (A) Heatmap showing differentially expressed genes in 17 paired tumor samples from Cohort 1, before and after CRT. (B) Volcano plot of deferentially expressed genes using −log10P value (Y-axis) and log2 fold change (X-axis), the red circles highlight genes with highest significance. (C) Pathway enrichment analysis of pre-RT vs on-RT DEGs, nGene Ratio and −log10 (q-value) are shown (D) Volcano plot of differentially expressed genes comparing Pre-RT and Mid-RT (third week of CRT) from Cosper et al., 2020, with −log10 P-value on the Y-axis and log2 fold change on the X-axis. The red circles highlight the most significantly altered gene. (E) Paired comparison of MDM2 transcript levels in cervical cancer patients before (Pre) and mid-treatment (Mid), from Cosper et al. (2020). Each line connects matched samples; the exact P-value from a two-tailed paired t-test is shown. (F) Pie Charts depicting the changes in tumor and immune cell populations over three time points in samples from Cohort 2. (G) Expression of viral proteins following CRT. (H) Ingenuity pathway prediction for MDM2 activation, according to the expression of its canonical associated transcription factors and target genes prominently expressed in tumor cells prior CRT. (I) Enrichment score of curated MDM2 pathways for each cell type across three different time points from Cohort 2. (J) Canonical pathway analysis of tumor cells pre-RT vs on-RT#2 time points (K) Network plot of the top significant regulators (P < 10−4) in tumor cells comparing pre-RT and on-RT#2 time points. The inner nodes represent groups of regulators with shared genetic influences, while the outer nodes indicate contributing marker genes. Symbols denote the following: - differentially expressed without a clear predicted direction, ▲ predicted upregulation (orange), and ▼ predicted downregulation (blue).