Extended Data Fig. 6: HNRNPC expression is associated with clinical outcomes in breast cancer patients.
From: An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus
(a) Distribution of 10-year relapse-free survival p-values (two-sided log rank test results reported as –log p for positive association and log p for negative) of the association of HNRNPC expression and clinical outcome in the listed 10 breast cancer datasets. Violet bars show associations that pass the statistical threshold (–log p < –1.3, FDR-corrected two-sided log-rank test (FDR < 0.1)), blue bars are trending negative, and yellow bars are trending positive. The statistical threshold was adjusted as 10/number of datasets. (b-c) Kaplan-Meier survival curves showing association between tumor HNRNPC levels and overall (b) or relapse-free (c) survival in a collection of breast cancer patient cohorts. Hazard ratios (HR) and p-values (calculated using log-rank test) are shown. (d) HNRNPC mRNA levels across breast tumor subtypes in the METABRIC cohort. Box center reports the median value, the boundaries - the quartiles, and the whiskers - the 10 and 90 percentiles. (e) Multivariate survival analysis (Cox proportionate-hazards model) of breast cancer patients in the METABRIC cohort with HNRNPC expression as one of the factors. P < 0.05 are highlighted in red. LumA, luminal A; LumB, luminal B; NC, not classified. (f-g) Kaplan-Meier survival curve showing association between tumor HNRNPC signature protein levels and progression-free (f) or overall (g) survival in the TCGA-BRCA CPTAC cohort. (h-j) Kaplan-Meier survival curve showing association between tumor PABPC4 (h) or PDLIM5 (i-j) levels and overall (h) or disease-free (i-j) survival in a collection of breast cancer patient cohorts. (k-l) Comparison of alternative polyadenylation ratio (logAPAR) in T4 and DMSO-treated MDA-MB-231 (k) or HNRNPC knockdown (sgHNRNPC) (l) cells, as in Fig. 2d. (m) Cumulative density plot of logAPAR comparing T4- to DMSO-treated HNRNPC knockdown (sgHNRNPC) cells, as in Extended Data Fig. 2e. (n) Dose-response measurements for 6-hour T4 treatment and corresponding cell viability, determined 72 hours post-treatment. n = 6 biological replicates. Mean values are plotted, error bars indicating SD. (o) Box plots illustrating the changes in alternative polyadenylation (logAPAR) of HNRNPC targets between T4-treated (sampled at indicated time points) and untreated MDA-LM2 cells. n = 3 biological replicates. p-values calculated using two-tailed Wilcoxon signed-rank test. Box plot characteristics as in (d).
