Figure 1 from The UBA1–STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade
Authors: Bao Yi , Cruz Gabriel , Zhang Yuping , Qiao Yuanyuan , Mannan Rahul , Hu Jing , Yang Fan , Gondal Mahnoor , Shahine Miriam , Kang Sarah , Mahapatra Somnath , Chu Alec , Choi Jae Eun , Yu Jiali , Lin Heng , Miner Stephanie J. , Robinson Dan R. , Wu Yi-Mi , Zheng Yang , Cao Xuhong , Su Fengyun , Wang Rui , Hosseini Noshad , Cieslik Marcin , Kryczek Ilona , Vaishampayan Ulka , Zou Weiping , Chinnaiyan Arul M. 
Published: February 2025

<p>High expression of <i>UBA1</i> is associated with low levels of intratumoral CD8<sup>+</sup> T cells and predictive of ICB resistance and poor survival in ICB cohorts. <b>A,</b> Left: Spearman correlation between mRNA expression of <i>IFNG</i> and 614 frequently gained genes in the indicated mCRPC cohort (<i>n</i> = 208). Genes that are significantly negatively correlated with <i>IFNG</i> mRNA expression are listed. Right: Spearman correlation between mRNA expression of the cytotoxic T-lymphocyte signature (<i>CD8A</i>, <i>CD8B</i>, <i>GZMA</i>, <i>GZMB</i>, and <i>PRF1</i>) and the genes listed on the left. SU2C, Stand Up to Cancer; PCF, Prostate Cancer Foundation. <b>B,</b> Spearman correlation between mRNA expression of <i>UBA1</i> and the indicated gene or gene signature in the indicated cohort. Eff., effector. <b>C,</b> Spearman correlation between <i>UBA1</i> copy number and mRNA expression in the indicated prostate cancer cohort. Frequency of copy number gain (gain) is shown. Patients with prostate cancer (male) with two or more copies of <i>UBA1</i> (on the X chromosome) are defined as gain. MCTP, The Michigan Center for Translational Pathology. <b>D,</b> Proportion of <i>UBA1</i> gain (left) and Spearman correlation between <i>UBA1</i> copy number and mRNA levels (right) in the indicated cancer types. Data were acquired from The Cancer Genome Atlas (TCGA). ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; COADREAD, colorectal adenocarcinoma; CSCC, cervical squamous cell carcinoma; EAC, esophageal adenocarcinoma; HCC, hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; OV, ovarian serous cystadenocarcinoma; SARC, sarcoma; STAD, stomach adenocarcinoma; UCS, uterine carcinosarcoma. <b>E,</b> Spearman correlation between pretreatment mRNA expression of <i>UBA1</i> and the indicated gene or signature, in a cohort treated with ICB at the U-M, Ann Arbor (MI-ONCOSEQ ICB cohort). <b>F,</b> Representative images (left) or quantification (Spearman correlation; right) of immunofluorescence assessing the number of CD8<sup>+</sup> T cells and the level of UBA1 in a melanoma tissue microarray (TMA). Scale bar, 50 μm. <b>G,</b> Fisher exact test of a combined analysis on four public RNA-seq datasets [Van Allen and colleagues (<a href="#bib34" target="_blank">34</a>); Zhao and colleagues (<a href="#bib35" target="_blank">35</a>); Miao and colleagues (<a href="#bib36" target="_blank">36</a>); and Jung and colleagues (<a href="#bib37" target="_blank">37</a>)] examining the relationship between pretreatment mRNA expression of <i>UBA1</i> and response to ICB. <b>H,</b> Uniform Manifold Approximation and Projection (UMAP) of malignant cells from scRNA-seq data in an ICB-treated melanoma cohort. Cells with high levels of pretreatment <i>UBA1</i> mRNA expression are highlighted in pink. PT#, patient number. <b>I,</b> Overall survival of patients with tumors showing high or low pretreatment: <i>UBA1</i> mRNA levels in the indicated cohorts. ccRCC, clear-cell renal cell carcinoma. Statistics were acquired by two-tailed Student’s <i>t</i> test in <b>H</b>, and by log-rank test in <b>I</b>.</p>