N6-methyladenosine (m6A) regulator expression pattern correlates with the immune landscape in lung adenocarcinoma.

Lung adenocarcinoma is the leading cause of tumor-related death. The tumor microenvironment (TME) may determine anti-tumor treatment responses. We focused on 23 m6A regulators, and analyzed m6A regulator expression patterns in 995 lung adenocarcinoma samples collected from 7 publicly available datasets. Two m6A clusters were identified, wherein gene clusters and m6A score were generated using unsupervised clustering and principal component analysis based on differentially expressed genes with prognostic significance. Further, three independent datasets from TCGA-LUAD and GEO were employed to validate the impact of m6A signatures and score. We found that m6A cluster 1 with high m6A score was associated with an inflamed TME, higher neoantigen and tumor mutation burden and improved response to immunotherapy. However, anti-tumor immunity cells were exhausted in high m6A score patients; thus, the prognosis of these patients was poor. Elucidation of m6A regulator expression pattern may facilitate the development of effective treatment strategies for lung adenocarcinoma.

Reference values of respiratory impedance with impulse oscillometry in healthy Chinese adults.

BACKGROUND: Impulse oscillometry (IO) is a non-invasive pulmonary function test for measuring respiratory impedance. Available reference equations of IO indices for adults are limited. The aim of this study was to develop reference equations of IO indices for Chinese adults. METHODS: In a multicentral, cross-sessional study of IO in Chinese adults, IO data from healthy subjects were collected from 19 general hospitals across China between 2016 and 2018. Oscillometry measurements were conducted in accordance with recommendations of the European Respiratory Society (ERS). Multiple linear regression was performed to develop sex-specific reference equations of IO indices. RESULTS: IO measurements were performed in 1,318 subjects, of which 567 subjects were defined as healthy individuals with acceptable IO data and were included in the final analysis. Reference equations and limits of normal [lower limit of normal (LLN)/upper limit of normal (ULN)] of IO indices were developed separately for males and females. Height but not age was shown to be the most influential contributor to IO indices. The reference equations currently used in lung function laboratories predicted higher R5 and X5. Normal ranges of R5 and X5 recommended by the equipment manufacturer were clearly different from the ULN/LLN derived from the reference equations. CONCLUSIONS: Reference equations of IO indices for Chinese adults from a wide region were provided in this study. It is necessary to update new IO reference equations and adopt ULN/LLN as normal ranges of IO indices. TRIAL REGISTRATION: This study was registered at www.clinicaltrials.gov as part of a larger study NCT03467880.

Mutational landscape and clonal diversity of pulmonary adenoid cystic carcinoma.

Pulmonary adenoid cystic carcinoma is a rare and indolent lung malignancy, characterized by a protracted but unpredictable growth behavior. Currently, the treatment of PACC relies on surgery and local radiotherapy. However, treatment options for advanced PACC patients are limited. A larger number of studies demonstrated that advanced PACC patients obtained limited benefit from chemotherapy. Moreover, only a few case reports revealed PACC patients were candidates for target therapy. Therefore, there is an urgent need to develop novel therapies. Due to its rareness, its mutational landscape remains largely elusive. In this study, we performed capture-based ultra-deep sequencing on multiregional surgical specimens obtained from 8 PACC patients using a panel consisting of 295 cancer-related genes. Our data revealed distinctive mutational spectrum of PACC, which differed from non-small cell lung cancer and adenoid cystic carcinomas originated from other anatomical sites. PACC, lacking mutations in a majority of non-small cell lung cancer driver genes, has frequent mutations in genes participating in chromatin remodeling and NOTCH signaling pathway. We also elucidated spatial intra-tumoral heterogeneity, which varied among cases. Most mutations in chromatin remodelers were subclonal. Collectively, our findings elucidated molecular signature associated with PACC and highlighted the potential for epigenetic therapy in this disease.