Assessment of circularized E7 RNA, GLUT1, and PD-L1 in anal squamous cell carcinoma

// Bahir H. Chamseddin 1 , Eunice E. Lee 1 , Jiwoong Kim 2 , Xiaowei Zhan 2 , Rong Yang 1 , Kathleen M. Murphy 3 , Cheryl Lewis 4 , Gregory A. Hosler 1 , 3 , * , Suntrea T. Hammer 5 , * and Richard C. Wang 1 , 3 , * 1 Department of Dermatology, UT Southwestern Medical Center, Dallas, 75390, TX, USA 2 Department of Clinical Science, UT Southwestern Medical Center, Dallas, 75390, TX, USA 3 ProPath Dermatopathology, Dallas, 75247, TX, USA 4 Harold C. Simmons Center, UT Southwestern Medical Center, Dallas, 75390, TX, USA 5 Department of Pathology, UT Southwestern Medical Center, Dallas, 75390, TX, USA * These authors contributed equally to this work Correspondence to: Richard C. Wang, email: richard.wang@utsouthwestern.edu Keywords: anal squamous cell carcinoma; circular RNA; GLUT1; human papillomavirus; PD-L1 Received: August 02, 2019 Accepted: September 23, 2019 Published: October 15, 2019 ABSTRACT Anal squamous cell carcinoma (ASCC) is a rare, potentially fatal malignancy primarily caused by high-risk human papillomaviruses (HPV). The prognostic implication of programmed death-ligand 1 (PD-L1) expression remains controversial, and glucose transporter 1 (GLUT1) expression has never been examined in ASCC. Covalently closed circular RNAs have recently been shown to be widespread in cancers and are proposed to be biomarkers. We discovered HPV16 expresses a circular E7 RNA (circE7) which has not been assessed as a potential biomarker. A retrospective, translational case series at UT Southwestern was conducted to analyze PD-L1, GLUT1, HPV-ISH, and HPV circE7 in relation to the clinical features and overall survival of patients with ASCC. Twenty-two (22) subjects were included in the study. Improved overall survival was predicted by basaloid histology ( p = 0.013), PD-L1 expression ( p = 0.08), and HPV-ISH positivity ( p < 0.001), but not GLUT1 expression. High levels of circE7 by quantitative RT-PCR predicted improved overall survival in ASCC ( p = 0.023) and analysis of The Cancer Genome Atlas sequencing from HPV-positive head and neck cancer and cervical cancer suggested high circE7 marked improved survival in 875 subjects ( p = 0.074). While our study suggests that circE7 levels correlate with improved survival in ASCC, larger, prospective studies are necessary to confirm the potential role of circE7 as a biomarker.