Overexpression of Human Aspartyl (Asparaginyl) β-hydroxylase in NSCLC: Its Diagnostic Value by Means of Exosomes of Bronchoalveolar Lavage

Abstract

The human aspartyl β-hydroxylase (ASPH) is overexpressed in tumor tissues. Bronchoalveolar lavage (BAL) is a diagnostic procedure for infections and malignancies. The aim of this study was to investigate whether tumor exosomes carrying ASPH gene marker were present in bronchoalveolar fluid of patients with non-small cell lung cancer (NSCLC). A tissue microarray analysis was applied to explore the expression of ASPH in different histologic NSCLC. The human NSCLC cell lines and normal bronchial cell lines were used to study exosomal ASPH exprerssion. A total of 27 NSCLC, 21 benign tumor, and 15 healthy controls underwent BAL. Immunohistochemistry was performed to study the ASPH expression in malignant and normal lung tissues. The expression characteristics of ASPH in different NSCLC and normal bronchial cells and pneumocytes were confirmed by cell blocks. A reverse transcription-quantitative polymerase chain reaction was carried out to study the levels of exosomal ASPH expression. Immunohistochemical staining of tissue microarray demonstrated that overexpression of ASPH was found in NSCLC tissues including adenocarcinoma, large cell carcinoma, and squamous cell carcinoma, but absent in adjacent normal tissues. All NSCLC specimens exhibited high levels of ASPH immunoreactivity, while nonmalignant and normal lung tissues exhibited a very low level of expression. Overexpression of ASPH was found in exosomes from NSCLC cell lines but absent from the normal bronchial cell line NL-20. ASPH level from BAL exosomes was significantly increased in NSCLC patients compared with that from nonmalignant or health group. Our method of isolation of BAL exosomes was easily performed in the clinical laboratory. BAL exosomal ASPH can be a potential biomarker for NSCLC diagnosis.

Transcriptomics secondary analysis of severe human infection with SARS-CoV-2 identifies gene expression changes and predicts three transcriptional biomarkers in leukocytes

“…The ASPH and C5orf30 gene products, which were identified as highly significant DEGs in our study, have been identified previously as markers of severe infection [58] . ASPH has also been identified as a marker in various cancers [59] , [60] , [61] , and likely alters Calcium homeostasis [62] . The C5orf30 gene product has been identified as a marker of rheumatoid arthritis severity [63] , [64] , suggesting an effect on cell migration, immunity, and inflammation.…”

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

“…Expression of apoptosis blocking bcl-2 protein predicts a poor prognosis for radiation-treated NSCLC patients [ 84 ]. Bronchoalveolar lavage (BAL)-exosomal human aspartyl β-hydroxylase (ASPH) is a potential biomarker for NSCLC diagnosis [ 85 ].…”