Correlation analysis of mesenchymal-epithelial transition factor protein and human epidermal growth receptor 2 protein expression in 1479 cases of lung adenocarcinoma in China

Introduction. Although cetuximab has been widely used in the treatment of colon cancer, a large number of patients eventually develop drug resistance. Therefore, it is essential to clarify the mechanism of drug resistance. Methods. In this study, we combined in silico analysis and a single guide RNA (sgRNA) library to locate cetuximab-sensitive genes. Cell proliferation, apoptosis, and cell cycle were assessed to validate the change in cetuximab sensitivity. Finally, western blotting was performed to detect changes in epidermal growth factor (EGFR) upstream and downstream genes. Results. Using in silico analysis and the sgRNA library, MEIS3 was confirmed as the cetuximab-sensitive gene. Further experiments indicated that the expression of MEIS3 could determine the level of cetuximab. Meanwhile, MEIS3-inhibited cells were sensitive to mesenchymal epithelial transition factor (c-Met) and protein kinase B (Akt) inhibitors, which is related to the change in phosphorylation of c-Met and degradation of Akt. Conclusion. MEIS3 modified the sensitivity to cetuximab through c-Met and Akt.

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A Novel c-Mesenchymal-Epithelial Transition Factor Intergenic Fusion Response to Crizotinib in a Chinese Patient With Lung Adenocarcinoma: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.727662 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hongge Liang ◽

Dexun Zhou ◽

Lin Dai ◽

Moqin Zhang ◽

Zhancheng Gao ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Adenocarcinoma ◽

Lung Disease ◽

Lower Lobe ◽

Tyrosine Kinase Receptor ◽

Carcinogenic Activity ◽

First Case ◽

Mesenchymal Epithelial Transition Factor ◽

Factor C ◽

Mesenchymal Epithelial Transition

BackgroundThe c-mesenchymal–epithelial transition factor (C-MET) is an oncogene encoding a tyrosine kinase receptor that plays an important role in tumor growth and metastasis. The National Comprehensive Cancer Network (NCCN) guidelines have approved carbatinib/crizotinib for advanced non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping.MethodsIn June 2020, the Department of Respiratory and Critical Care Medicine of Peking University People’s Hospital admitted a 72-year-old male patient with lung adenocarcinoma (LADC) with a history of interstitial lung disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis. Genetic examination by next-generation sequencing showed an intergenic fusion of MET, and crizotinib was administered on August 14, 2020. Follow-up showed that tumor volume was significantly reduced. However, crizotinib was discontinued in November 2020 because of the patient’s worsening interstitial lung disease, and CT scans showed continued partial response (PR) for 5 months. In April 2021, right lower lobe mass progressed, and disease progression was considered.ConclusionThis was the first case of a patient with LADC with MET intergenic fusion who significantly benefited from crizotinib. Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.

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