第860回千葉医学会例会・第16回千葉大学放射線医学教室例会

Methylation pattern in tumours and normal tissues. The methylation signature of RASSF1Îą, TIMP3 and PCQAP in HNSCC and normal tissues from The Cancer Genome Atlas (TCGA) database. (DOCX 91 kb

Additional file 1: of Network analysis of an in vitro model of androgen-resistance in prostate cancer

Table S1.  Top 15 pathways for the human differentially expressed genes. Table S2. Top 15 pathways for the cell line deferentially expressed genes. Figure S1. Differencially expressed cell line genes overlaid on KEGG hsa04010 MAPK signaling pathway. Figure S2. Differentially expressed cell line genes overlaid on KEGG hsa04151 PI3K-Akt signaling pathway-Homo sapiens (human). Figure S3. Differentially expressed human tumour genes overlaid on KEGG hsa04010 MAPK signaling pathway. Figure S4. Differentially expressed human tumour genes overlaid on KEGG hsa04151 PI3K-Akt signaling pathway-Homo sapiens (human). (PDF 460 kb

Additional file 1: Figure S1. of Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers

MED15/PCQAP MSP amplicon sequence confirmation. The alignment of MED15/PCQAP MSP amplicon sequence in the NCBI Basic Local Alignment Search Tool (BLAST) database. (DOCX 218 kb

Additional file 3: Figure S2. of Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers

The amplification regions of individual genes with respective promoter start sites and CpG islands. A detailed map illustrating the location of the amplification region, promoter start site and CpG islands for RASSF1Îą, p16 INK4a , TIMP3 and PCQAP. (DOCX 260 kb

AR negative triple negative or “quadruple negative” breast cancers in African American women have an enriched basal and immune signature

<div><p>There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered “Quadruple negative” Breast Cancers (“QNBC”). However, a comprehensive analysis of AR expression within all breast cancer subtypes or stratified by race has not been reported. We assessed AR mRNA expression in 925 tumors from The Cancer Genome Atlas (TCGA), and 136 tumors in 2 confirmation sets. AR protein expression was determined by immunohistochemistry in 197 tumors from a multi-institutional cohort, for a total of 1258 patients analyzed. Cox hazard ratios were used to determine correlations to PAM50 breast cancer subtypes, and TNBC subtypes. Overall, AR-negative patients are diagnosed at a younger age compared to AR-positive patients, with the average age of AA AR-negative patients being, 49. AA breast tumors express AR at lower rates compared to Whites, independent of ER and PR expression (p<0.0001). AR-negative patients have a (66.60; 95% CI, 32–146) odds ratio of being basal-like compared to other PAM50 subtypes, and this is associated with an increased time to progression and decreased overall survival. AA “QNBC” patients predominately demonstrated BL1, BL2 and IM subtypes, with differential expression of E<i>2F1</i>, <i>NFKBIL2</i>, <i>CCL2</i>, <i>TGFB3</i>, <i>CEBPB</i>, <i>PDK1</i>, <i>IL12RB2</i>, <i>IL2RA</i>, and <i>SOS1</i> genes compared to white patients. Immune checkpoint inhibitors PD-1, PD-L1, and CTLA-4 were significantly upregulated in both overall “QNBC” and AA “QNBC” patients as well. Thus, AR could be used as a prognostic marker for breast cancer, particularly in AA “QNBC” patients.</p></div

AR-associated genes.

<p>A. Genes most highly associated <i>(bivariate cutoff 1</i>.<i>0E-07)</i> with AR expression across the TCGA dataset were used to determined novel gene expression signatures associated with AR tumor status. Distinct subgroups of genes with shared expression trends were identified using K-means cluster analysis and separated into 5 nodes of genes with expression trends that are either upregulated or downregulated in the AR-negative tumors. B. A subset of genes related to the Immunomodulatory TNBC subtype display statistically significant differences in expression between AA vs White patients when comparing expression in AR-high and AR-low categories.</p

AR status is significantly different between race groups and among molecular subtypes.

<p>(A). AA women have more AR-negative tumor types in each molecular subtype. (B). Within the AR-negative subtypes, there are significantly higher proportions of TNBC basal-like. (C). All TNBC samples were subjected to “Vanderbilt” subtypes. AAs, compared to White AR-negative QNBC patients, had more BL1 (24% v 17%), BL2 (16% v 12%), and IM (24% v 19%) subtypes. Inversely, AR-negative White QNBC patients had more mesenchymal (M) (25% v 20%), mesenchymal stem-like (MSL) (12% v 8%), and unstable (UNS) (14% vs 8%) subtypes compared to AR-negative QNBC AA TNBC patients.</p

PAM50 and Vanderbilt gene expressions subtypes stratified by AR expression in total population (quartile).

<p>PAM50 and Vanderbilt gene expressions subtypes stratified by AR expression in total population (quartile).</p

Patient characteristics of TCGA population.

<p>The TCGA invasive breast cancer dataset had the largest patient set of RNA-seq data (primary breast cancers for 180 AAs and 745 Whites) was used to quantify distributions of AR expression across patient groups in order to calculate a suitable threshold to stratify the entire dataset/population as AR-positive or AR-negative categories, based on highest and lowest tertiles, exclusively.</p