FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC

• Main Authors: Sarah Richtmann, Dennis Wilkens, Arne Warth, Felix Lasitschka, Hauke Winter, Petros Christopoulos, Felix J. F. Herth, Thomas Muley, Michael Meister, Marc A. Schneider
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Cancers
• Subjects: NSCLC; FAM83A; FAM83B; biomarker; EGFR-TKI
• Online Access: https://www.mdpi.com/2072-6694/11/5/652

Although targeted therapy has improved the survival rates in the last decade, non-small-cell lung cancer (NSCLC) is still the most common cause of cancer-related death. The challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in epidermal growth factor receptor (EGFR) signaling. Here, gene expression of <i>FAM83A</i> and <i>B</i> was analyzed in a cohort of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value. Functional assays in NSCLC cell lines were performed to evaluate <i>FAM83A</i> and <i>B</i> involvement in proliferation, anchorage-independent growth, migration, and the EGFR pathway. We observed a highly increased gene expression level of <i>FAM83A</i> (&#248; = 68-fold) and <i>FAM83B</i> (&#248; = 20-fold) which resulted in poor survival prognosis (<i>p</i> &lt; 0.0001 and <i>p</i> = 0.002). Their expression was influenced by EGFR levels, pathway signaling, and mutation status. Both genes affected cell proliferation, and <i>FAM83A</i> depletion resulted in reduced migration and anchorage-independent growth. The results support the hypothesis that <i>FAM83A</i> and <i>B</i> have different functions in different histological subtypes of NSCLC and might be new therapeutic targets.