5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a catalysing enzyme in the de novo purine biosynthetic pathway, has been previously reported to be upregulated and to participate in myeloma and hepatocellular carcinoma progression. In the present study, by using bioinformatics technology, a higher ATIC expression was identified in lung adenocarcinoma (LUAD) tissues than in normal tissues, and ATIC expression was found to be positively associated with Myc expression in LUAD tissues. In addition, the role of ATIC in modulating the growth and migration of LUAD cells was explored and the involvement of Myc was revealed. ATIC expression in 56 paired LUAD and tumour adjacent non-cancerous tissues was assessed using reverse transcription-quantitative PCR and western blot analysis. Pearson's correlation analysis was applied to evaluate the correlation between ATIC and Myc expression levels in LUAD tissues. A rescue experiment was performed to explore the role of ATIC/Myc in regulating the growth, migration and invasion of HCC827 and NCI-H1435 cells. It was demonstrated that ATIC was overexpressed in LUAD tissues, particularly in advanced-stage LUAD, and was predicted to be associated with an advanced TNM stage, a higher lymph node metastasis rate, poor tissue differentiation and a lower overall survival rate. ATIC overexpression promoted cell growth, migratory and invasive capacities, whereas this effect was abrogated by Myc knockdown in the HCC827 and NCI-H1435 cells. On the whole, the present study demonstrates that ATIC promotes LUAD cell growth and migration by increasing Myc expression.
Background: Epidermal growth factor receptor (EGFR) exon 19 deletion (19del) and the exon 21 L858R point mutation are the most established predictive factors for the efficacy of EGFR-tyrosine kinase inhibitor (TKI) in patients with non-small cell lung cancer (NSCLC). To date, more than 50 subtypes of EGFR 19dels have been documented in NSCLC. Evidence suggests that different subtypes of 19dels exhibit different survival outcomes to EGFR-TKI treatment. Whether patients harboring EGFR Leu747_Ser752 deletion (delL747_S752) as an uncommon subtype of 19dels benefit from EGFR-TKIs has not been investigated. BIM (B-cell chronic lymphocytic leukemia/lymphoma-like 1) deletion polymorphism is common in East Asian with EGFR-mutant non-small-cell lung cancer (NSCLC). Currently, the predictive role of BIM deletion polymorphism in patients with EGFR-mutant NSCLC treated with osimertinib remains debatable. Case Description: A 34-year-old female patient was diagnosed with stage IV lung adenocarcinoma (LUAD) harboring somatic EGFR del L747_S752 and germline BIM deletion polymorphism in August 2018. She obtained benefit from the front-line treatment of osimertinib lasting for 8 months. After progression from osimertinib, the patient received bevacizumab combined with platinum-doublet chemotherapy, stereotactic radiosurgery plus osimertinib and crizotinib, anlotinib, and a programmed cell death-1 inhibitor sintilimab plus bevacizumab and docetaxel. She succumbed to her disease in June 2020 with an overall survival of 23 months. Conclusions: Our work suggests that osimertinib might be a compromised treatment option for NSCLC patients with somatic EGFR delL747_S752 and germline BIM deletion polymorphism. Development of more effective regimens are needed for this small subset of NSCLCs.
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