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. 2022 Jun 24;2(6):503–517. doi: 10.1158/2767-9764.CRC-22-0168

FIGURE 4.

FIGURE 4

Resptress score identifies distinct molecular subtypes among various cancer types. A, Repstress scores among different breast cancer molecular subtypes. ****, P < 0.0001 by one-way ANOVA followed by Tukey multiple comparison test. B, Repstress scores in pancreatic cancers with adenocarcinoma (PDAC) versus adenosquamous (AD/SC) histology. ****, P < 0.0001 by Mann–Whitney U test. C, Repstress scores in malignant mesothelioma with epithelioid (Epi) versus sarcomatoid or mixed epithelioid and sarcomatoid (Sarc) histology. **, P < 0.01 by Mann–Whitney U test. D, Repstress scores among prostate cancers with different Gleason scores. ****, P < 0.0001 by linear trend test from left to right. E, Repstress scores and somatic copy-number alterations (SCNA) of TCGA prostate cancers SCNA subtype are defined by copy number–based clustering in a previous report (64). ****, P < 0.0001 by linear trend test from left to right. F, Repstress scores among uterine corpus endometrial carcinomas with different SCNA subtypes. SCNA subtypes are defined by copy number–based clustering in a previous report (65). ****, P < 0.0001 by one-way ANOVA followed by Tukey multiple comparison test. G, Repstress scores among transcriptomic subtypes in ovarian carcinoma The molecular subtypes are defined on the basis of transcriptome-based clustering in a previous report (66). ****, P < 0.0001 by one-way ANOVA followed by Tukey multiple comparison test. H, Repstress scores among genomic subtypes in hepatocellular carcinoma. The molecular subtypes (iCluster) are defined on the basis of an integrative analysis of DNA copy number, DNA methylation, mRNA expression, miRNA expression, and RPPA in a previous report (67). ***, P < 0.001 by one-way ANOVA followed by Tukey multiple comparison test. I, Repstress scores between patients with HPV-null (HPV−) and HPV-driven (HPV+) head and neck cancers. ****, P < 0.0001 by unpaired Student t test. Correlations between gene expression of APOBEC3B and repstress score in breast cancer (J), lung adenocarcinoma (K), and acute myeloid leukemia (L). Repstress score comparison between tumors with KEAP1/STK11 coalterations compared with those without (M), and tumors with KRAS/STK11 coalterations compared with KRAS single-altered tumors (N) in lung adenocarcinoma. Gene alterations or copy-number deletion (either heterozygous or homozygous) are considered as genetically alteration in KRAS, KEAP1, and STK11. Lung adenocarcinoma with KRAS/TP53 or KRAS/CDKN2A comutations are excluded from the analysis in N given a previous study reporting that non–small cell lung cancer with these comutations is different subtype from KRAS/STK11 comutated subtype (71, 72). ****, P < 0.0001; **, P < 0.01 by Mann–Whitney U test. O, A schema of repstress gene signature characterizing replication stress and its response. TCGA, The Cancer Genomic Atlas; LumA, luminal A; LumB, luminal B; PDAC, pancreatic adenocarcinoma; AD/SC, adenosquamous; Epi, epithelioid; Sarc, sarcomatoid; GS, Gleason score; SCNA, somatic copy-number alteration; CN, copy number; POLE, DNA polymerase epsilon, catalytic subunit; MSI, microsatellite instable; HPV, human papillomavirus; APOBEC, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like; STK11, Serine/threonine kinase 11; KEAP1, Kelch-like ECH-associated protein 1; RS, replication stress. Abbreviations for cancer types in TCGA are available from https://gdc.cancer.gov/resources-tcga-users/tcga-code-tables/tcga-study-abbreviations.