ERBB2 mutation landscape in non-small cell lung cancer patients in Northeast China.

OBJECTIVE: This study aimed to explore erb-b2 receptor tyrosine kinase 2 (ERBB2) gene mutations in patients with non-small cell lung cancers (NSCLC) in Northeast China, and to analyze ERBB2 mutation subtypes and clinicopathological characteristics related to the presence of ERBB2 mutations. METHODS: In this study, 1087 tissue samples, 368 whole blood samples, and 68 pleural effusion samples from 1349 NSCLC were collected. Next-generation sequencing (NGS) was used to perform genetic testing on the samples. The proportion of patients with ERBB2 mutations and related clinicopathological characteristics were analyzed. RESULTS: The mutation rate of ERBB2 in NSCLC was 5.58% (85/1523). Of the patients with ERBB2 mutations, 27.63% (21/76) were over 65 years old, 59.21% (45/76) were women, and 68.42% (52/76) were non-smokers. The majority of tumors were adenocarcinomas (92.1%, 70/76) and stage III and IV diseases accounted for 81.58% (62/76) of all cases. There were 14 subtypes of ERBB2 mutations; the most frequently seen were ERBB2 copy number alteration (41.76%, 38/91) and ERBB2 exon 20 in-frame insertion (36.26%, 33/91). Of the patients with ERBB2 mutations, 24 had concurrent epidermal growth factor receptor mutations, seven had mesenchymal epithelial transition factor amplifications, and three had anaplastic lymphoma kinase mutations. The agreement between tissue and paired blood samples in the presence of ERBB2 mutations was 64.3% (9/14). CONCLUSION: ERBB2 mutations in Northeast China NSCLC patients have a unique molecular spectrum. Our work can provide guidance for the clinical diagnosis and treatment of patients with ERBB2 mutations in Northeast China.

Long Noncoding RNA LINC01426 Sequesters microRNA-519d-5p to Promote Non-Small Cell Lung Cancer Progression by Increasing ETS1 Expression.

PURPOSE: Recent studies have identified important roles for long intergenic non-protein coding RNA 1426 (LINC01426) in glioma and clear cell renal cell carcinoma. The present study evaluated the expression profile of LINC01426 in non-small cell lung cancer (NSCLC) tissues and cell lines. Furthermore, the function of LINC01426 in NSCLC and the molecular mechanisms involved were extensively studied. METHODS: The abundance of LINC01426 in NSCLC tissues and cell lines was determined using quantitative reverse transcription-polymerase chain reaction. The cell counting kit-8 assay, flow cytometry, transwell experiments for migration and invasion, and xenograft tumor model were used to assess the function of LINC01426 in NSCLC cells. Mechanistic studies were performed using the luciferase reporter assay and RNA immunoprecipitation. RESULTS: Significant LINC01426 upregulation was observed in NSCLC tissues and cell lines. Silencing LINC01426 inhibited proliferation, migration, and invasion of NSCLC cells and facilitated cell apoptosis in vitro. Furthermore, interference of LINC01426 restricted tumor growth of NSCLC cells in vivo. In addition, LINC01426 showed the ability to directly bind to microRNA-519d-5p (miR-519d-5p) and act as a molecular sponge for miR-519d-5p in NSCLC cells. Furthermore, the ETS proto-oncogene 1 (ETS1) was identified as a direct target of miR-519d-5p and LINC01426 could indirectly upregulate ETS1 expression by sponging miR-519d-5p. Moreover, the cancer-inhibiting activities of LINC01426 knockdown in NSCLC cells were partially offset by miR-519d-5p inhibition. CONCLUSION: LINC01426 increases ETS1 expression by sequestering miR-519d-5p, thereby aggravating the malignant progression of NSCLC. The LINC01426/miR-519d-5p/ETS1 competing endogenous RNA pathway may provide a target for designing therapeutic agents for NSCLC treatment.