Identification of heritable rare variants associated with early-stage lung adenocarcinoma risk

Abstract

Background: In East Asia, the number of patients with adenocarcinoma, especially those presenting with ground-glass nodules (GGNs), is gradually increasing. Family aggregation of pulmonary GGNs is not uncommon; however, genetic predisposition in these patients remains poorly understood and identification of genes involved in the cause of these early-stage lung cancers might contribute to understanding of the underlying mechanisms and potential prevention strategies.Methods: Fifty patients with early-stage lung adenocarcinoma (LUAD) presenting as GGNs and a firstdegree family history of lung cancer (FHLC) from 34 independent families were enrolled into this study. Germline mutations of these patients were analyzed with whole exome sequencing (WES) and compared with age-and sex-matched 39 patients with sporadic lung cancer and 689 local healthy people. We used a stepwise variant filtering strategy, gene-based burden testing, and enrichment analysis to investigate rare but potentially pathogenic heritable mutations. Somatic tumor mutations were analyzed to consolidate germline findings.Results: In total, 1,571 single nucleotide variants (SNVs) and 238 frameshifts with a minor allele frequency (MAF) <0.01, which were rare, recurrent, and potentially damaging candidates, were finally identified through the filtering in the GGN cohort. Pathway analysis showed the extracellular matrix to be the top dysregulated pathway. Gene-based burden testing of these highly disruptive risk-conferring heritable variants showed that MSH5 [odds ratio (

Cuproptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of early-stage lung adenocarcinoma patients

“…Recently, diagnostic tests for detecting early-stage lung cancer are chest low dose computerized tomography (LDCT) and chest X-rays. However, some es-LUAD patients still have recurrence and metastasis beyond receiving the recommending treatment of the clinical guidelines ( Nooreldeen and Bach, 2021 ; Fu et al, 2022 ; James et al, 2022 ). Discovery of new diagnostic tools is essential for evaluating cancer prognosis.…”

The influence of baseline characteristics on the efficacy of immune checkpoint inhibitors for advanced lung cancer: A systematic review and meta-analysis

“…This mechanism may improve the reaction of immunotherapy. On the other hand, from the point of pathological type, patients with smoking history took higher risks on suffering from squamous cell carcinoma ( Park et al, 2010 ), while non-smokers may have higher genetic susceptibility to adenocarcinoma ( Fu et al, 2022 ). The research by Tian et al (2021) indicated that patients with squamous cell carcinoma may obtain more lasting OS from ICIs than those with adenocarcinoma.…”

A Systematic Study of Traditional Chinese Medicine for the Treatment of Lung Adenocarcinoma Using a Reverse Network of Key Targets Based on Bioinformatics and Molecular Docking: Curcumin and Trans-Resveratrol as Potential Drug Candidates for Lung Adenocarcinoma

“…25 In addition, with certain diseases or age, MMPs could be a characteristic of cancer. 26 CD44 was a non-kinase transmembrane glycoprotein that promoted cancer cell proliferation and invasion. 27 The expression level of CD44 was down-regulated in LUAD tissues, and the low CD44 expression group had a poor prognosis.…”