SARS-CoV-2-correlated ASGR1 is a novel potential marker for the treatment and identification of multiple human cancers

ABSTRACT

Objectives: Cancer patients are reported to be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the COVID-19 (the Corona Virus Disease 2019) patients with cancer suffer from certain serious complications. ASGR1 has been recently identified as a novel receptor of SARS-CoV-2 in human cells;however, there are limited studies on ASGR1 in various human cancers. Method(s) This study utilized a comprehensive analysis of COVID-19-related ASGR1 in multiple human cancers based on 18,589 multi-center samples. Using Wilcoxon rank-sum analysis, a difference in ASGR1 expression between cancer and control tissues was detected. Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were utilized to determine the correlation between ASGR1 expression and the clinical parameters of cancer patients. The immune relevance and potential mechanisms of ASGR1 in various cancers were also investigated. Result(s) Abnormal ASGR1 mRNA expression was observed in 16 of 20 different cancers (e.g., it was upregulated in colon adenocarcinoma but downregulated in cholangiocarcinoma;P < 0.05). ASGR1 was related to prognosis, e.g., overall survival, in 14 cancers (P < 0.05), such as adrenocortical carcinoma. The gene was also found to be a potential marker that can be utilized to distinguish eleven cancers from controls with moderate to high accuracy (e.g., the area under the curve for cholangiocarcinoma = 1.000). ASGR1 expression was related to DNA methyltransferases, mismatch repair genes, immune checkpoints, levels of tumor mutational burden, microsatellite instability, neoantigen count, and immune infiltration levels in certain cancers (P < 0.05). The gene plays a role in multiple cancers by affecting four signaling pathways, such as cytokine-cytokine receptor interaction. Cancer patients with high ASGR1 expression are sensitive to 25 drugs, including ulixertinib. Conclusion(s) SARS-CoV-2-correlated ASGR1 is a novel marker that can be used for treating and identifying multiple human cancers. Copyright © 2022 E-Century Publishing Corporation. All rights reserved.