Research Papers:

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

Bahir H. Chamseddin, Eunice E. Lee, Jiwoong Kim, Xiaowei Zhan, Rong Yang, Kathleen M. Murphy, Cheryl Lewis, Gregory A. Hosler, Suntrea T. Hammer and Richard C. Wang _

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Oncotarget. 2019; 10:5958-5969. https://doi.org/10.18632/oncotarget.27234

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Bahir H. Chamseddin1, Eunice E. Lee1, Jiwoong Kim2, Xiaowei Zhan2, Rong Yang1, Kathleen M. Murphy3, Cheryl Lewis4, Gregory A. Hosler1,3,*, Suntrea T. Hammer5,* and Richard C. Wang1,3,*

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: [email protected]

Keywords: anal squamous cell carcinoma; circular RNA; GLUT1; human papillomavirus; PD-L1

Received: August 02, 2019     Accepted: September 23, 2019     Published: October 15, 2019


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.

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