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. 2018 Sep 4;13(9):e0203397. doi: 10.1371/journal.pone.0203397

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© 2018 Mon et al

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Fig 7 — (A) Immunohistochemical analysis of VRK1 expression in breast tissue microarray. VRK1 score was determined by multiplying the VRK1 staining intensity × percentage of VRK1 positive staining. Fig 8A includes the data from all primary tumor and lymph node samples. Bars indicate the median. (Mann-Whitney test, ***p<0.001). (B) VRK1 protein expression is higher in the vast majority of lymph node metastases (24 of 28) than in patient-matched primary tumors. (C) Oncomine.org was used to probe the complete Curtis Breast dataset (2,136 samples) in order to determine whether the VRK1 mRNA was within the top 10% of overexpressed transcripts in breast cancer samples vs. normal breast tissue. The overall median rank of VRK1 mRNA overexpression was 947 (out of 19,273 measured genes) (p = 3.64x10^-28). Data for cancer subtypes are shown in boxes numbered 1–11: 1: benign breast neoplasm (rank 6459, 1.4 fold-change, NS), 2: breast carcinoma (rank 833, 1.5 fold-change, p = 3.83x10^-5), 3: breast phyllodes tumor (rank 512, 1.2 fold-change, p = 0.002), 4: ductal breast carcinoma in situ (rank 1969, 1.5 fold-change, p = 0.002), 5: invasive breast carcinoma (rank 1060, 1.6 fold-change, p = 1.28x10^-5), 6: invasive ductal and invasive lobular breast carcinoma (rank 941, 1.5 fold-change, p = 6.76x10^-22), 7: invasive ductal breast carcinoma (rank 613, 1.5-fold change, p = 2.71x10^-71), 8: invasive lobular breast carcinoma (rank 947, 1.3 fold-change, p = 3.64x10^-28), 9: medullary breast carcinoma (rank 400, 1.8 fold-change, p = 3.25x10^-12), 10: mucinous breast carcinoma (rank 1932, 1.4 fold-change, p = 7.41x10^-10) and 11: tubular breast carcinoma (rank 1253, 1.4 fold-change, p = 1.24x10^-17). The median rank of overexpression is shown by the spectrum of white-pink-red colors shown in the legend; VRK1 is in the top 5% of overexpressed mRNAs in subsets 2,3,6–9 and in the top 10% of overexpressed mRNAs in subsets 5 and 11. (D-F) Correlation of VRK1 overexpression and decreased relapse-free survival of breast cancer patients. Data analysis using Kaplan-Meier plotter reveal the probability of relapse-free survival for 3,951 breast cancer patients with low (black line) or high (red line) VRK1 expression. (D) HR [hazard ratio] of 1.72, p<1x10^-16). (E) Similar analysis of 2,061 patients with ER⁺ breast cancer (HR 1.48, p = 5.5x10^-6). (F) Similar analysis of 801 patients with ER- breast cancer (HR 1.05, p = 0.65). A significant correlation between high VRK1 expression and reduced relapse–free survival is seen for patients with ER+ breast cancer.