Yan Zhao

A Comprehensive and Systematic Analysis Revealed the Role of ADAR1 in Pan-Cancer Prognosis and Immune Implications

Adenosine deaminase RNA specific 1 (ADAR1) has been identified as an enzyme that deaminates adenosine within the dsRNA region to produce inosine, whose amplification reinforced the exhaustion of the immune system. Although there were currently cellular and animal assays supporting the relationship between ADAR1 and specific cancers, there was no correlation analysis that has been performed at the pan-cancer level. Therefore, we first analyzed the expression of ADAR1 in 33 cancers based on the TCGA (The Cancer Genome Atlas) database. ADAR1 was highly expressed in most cancers, and there was a closely association between ADAR1 expression and prognosis of patients. Furthermore, pathway enrichment analysis revealed that ADAR1 was involved in multiple antigens presenting and processing inflammatory and interferon pathways. Moreover, ADAR1 expression was positively correlated with CD8+ T cell infiltration levels in renal papillary cell carcinoma, prostate cancer, and endometrial cancer and negatively correlated with Treg cell infiltration. In addition, we further found that ADAR1 expression was closely associated with various immune checkpoints and chemokines. Meanwhile, we observed that ADAR1 may be involved in the regulation of pan-cancer stemness. In conclusion, we provided a comprehensive understanding of the oncogenic role of ADAR1 in pan-cancer, and ADAR1 might serve as a new potential target for antitumor therapy.

Comparing the Diagnostic Performance of Quantitative PCR, Digital Droplet PCR, and Next-Generation Sequencing Liquid Biopsies for Human Papillomavirus–Associated Cancers

Human papillomavirus (HPV)-associated cancers, including oropharyngeal squamous cell carcinoma (HPV + OPSCC), cervical cancer, and squamous cell carcinoma of the anus (HPV + SCCA), release circulating tumor HPV DNA (ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches used and the individual assay metrics. A comparison of these approaches has not been systematically performed to inform expected performance, which in turn affects clinical interpretation. A meta-analysis was performed using Ovid MEDLINE, Embase, and Web of Science Core Collection databases to assess the diagnostic accuracy of ctHPVDNA detection across cancer anatomic sites, detection platforms, and blood components. The population included patients with HPV + OPSCC, HPV-associated cervical cancer, and HPV + SCCA with pretreatment samples analyzed by quantitative PCR (qPCR), digital droplet PCR (ddPCR), or next-generation sequencing (NGS). Thirty-six studies involving 2986 patients met the inclusion criteria. The sensitivity, specificity, and quality of each study were assessed and pooled for each analysis. The sensitivity of ctHPVDNA detection was greatest with NGS, followed by ddPCR and then qPCR when pooling all studies, whereas specificity was similar (sensitivity: ddPCR > qPCR, P  ddPCR, P = 0.014). ctHPVDNA from OPSCC was more easily detected compared with cervical cancer and SCCA, overall (P = 0.044). In conclusion, detection platform, anatomic site of the cancer, and blood component used affects ctHPVDNA detection and must be considered when interpreting results. Plasma NGS-based testing may be the most sensitive approach for ctHPVDNA overall.