Figure 4 from Concurrent RB1 Loss and <i>BRCA</i> Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma
Authors: Saner Flurina A.M. , Takahashi Kazuaki , Budden Timothy , Pandey Ahwan , Ariyaratne Dinuka , Zwimpfer Tibor A. , Meagher Nicola S. , Fereday Sian , Twomey Laura , Pishas Kathleen I. , Hoang Therese , Bolithon Adelyn , Traficante Nadia , Alsop Kathryn , Christie Elizabeth L. , Kang Eun-Young , Nelson Gregg S. , Ghatage Prafull , Lee Cheng-Han , Riggan Marjorie J. , Alsop Jennifer , Beckmann Matthias W. , Boros Jessica , Brand Alison H. , Brooks-Wilson Angela , Carney Michael E. , Coulson Penny , Courtney-Brooks Madeleine , Cushing-Haugen Kara L. , Cybulski Cezary , El-Bahrawy Mona A. , Elishaev Esther , Erber Ramona , Gayther Simon A. , Gentry-Maharaj Aleksandra , Gilks C. Blake , Harnett Paul R. , Harris Holly R. , Hartmann Arndt , Hein Alexander , Hendley Joy , Hernandez Brenda Y. , Jakubowska Anna , Jimenez-Linan Mercedes , Jones Michael E. , Kaufmann Scott H. , Kennedy Catherine J. , Kluz Tomasz , Koziak Jennifer M. , Kristjansdottir Björg , Le Nhu D. , Lener Marcin , Lester Jenny , Lubiński Jan , Mateoiu Constantina , Orsulic Sandra , Ruebner Matthias , Schoemaker Minouk J. , Shah Mitul , Sharma Raghwa , Sherman Mark E. , Shvetsov Yurii B. , Soong T. Rinda , Steed Helen , Sukumvanich Paniti , Talhouk Aline , Taylor Sarah E. , Vierkant Robert A. , Wang Chen , Widschwendter Martin , Wilkens Lynne R. , Winham Stacey J. , Anglesio Michael S. , Berchuck Andrew , Brenton James D. , Campbell Ian , Cook Linda S. , Doherty Jennifer A. , Fasching Peter A. , Fortner Renée T. , Goodman Marc T. , Gronwald Jacek , Huntsman David G. , Karlan Beth Y. , Kelemen Linda E. , Menon Usha , Modugno Francesmary , Pharoah Paul D.P. , Schildkraut Joellen M. , Sundfeldt Karin , Swerdlow Anthony J. , Goode Ellen L. , DeFazio Anna , Köbel Martin , Ramus Susan J. , Bowtell David D.L. , Garsed Dale W. 
Published: August 2024

<p>Characterization of HGSC with co-loss of RB1 and <i>BRCA</i>. <b>A,</b> GSEA indicating up- and downregulated pathways in tumors according to <i>BRCA</i> and <i>RB1</i> status. <i>RB1</i>-alt, <i>RB1</i> altered; <i>RB1</i>-wt, <i>RB1</i> wild-type. <b>B,</b> Boxplots comparing GSVA pathway enrichment scores of the cGAS-STING and Toll-like receptor signaling pathways between molecular subgroups; points represent each sample, boxes show the interquartile range (25th–75th percentiles), central lines indicate the median, and whiskers show the smallest/largest values within 1.5 times the interquartile range. Colored boxes with black points indicate the HRD and/or <i>RB1</i> altered groups, whereas the gray boxes with gray points indicate the HRP and <i>RB1</i> wild-type group. <i>P</i> values were calculated using a two-sided Mann–Whitney-Wilcoxon test. Benjamini–Hochberg adjusted <i>P</i> values are shown above each pairwise comparison (*, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ns, <i>P</i> ≥ 0.05). <b>C,</b> Bubble plot summary of <i>HLA</i> gene expression comparisons using DESeq2 between HGSC tumors grouped by HRD and/or <i>RB1</i> status as shown. The size of the bubbles corresponds to the negative log<sub>10</sub> Benjamini–Hochberg adjusted <i>P</i> value (<i>P</i><sub>adj</sub>) and only values with <i>P</i><sub>adj</sub> ≤ 0.1 are shown. The color and intensity correspond to the log<sub>2</sub>fold change. Genes are grouped by their classes. <b>D,</b> Proportion of TILs in HGSC tumors grouped by RB1 protein expression and <i>BRCA</i> germline status. <i>χ</i><sup>2</sup><i>P</i> value is indicated. <b>E,</b> Proportion of tumors classified as each HGSC molecular subtype (<a href="#bib13" target="_blank">13</a>) grouped by RB1 expression and <i>BRCA</i> germline status. χ<sup>2</sup><i>P</i> value is indicated. C4.DIF, C4/differentiated subtype; C2.IMM, C2/immunoreactive subtype; C1.MES, C1/mesenchymal subtype; C5.PRO, C5/proliferative subtype.</p>