Telomere-Related Gene Mutations and Lung Diseases: Pulmonary Fibrosis, Emphysema and Lung Cancer

Idiopathic pulmonary fibrosis (IPF) represents one of the most common chronic interstitial lung diseases. Usual interstitial pneumonia (UIP) is the pathologic diagnosis of IPF and can be diagnosed when honeycombing is present with a basilar and peripheral predominance and findings not typical of UIP are absent. In the current era, when a diagnosis of UIP is made with confidence on HRCT, biopsy can be avoided. Yet, one must be familiar with mimics of UIP/IPF (most notably pulmonary edema superimposed on emphysema) to avoid confusion misdiagnosis. Radiologists must also be familiar with potential complications of UIP including progression, infection, accelerated fibrosis (which can be lethal) and primary lung cancer (which has an increased incidence in UIP).

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Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105825 ◽

2019 ◽

Vol 56 (10) ◽

pp. 647-653 ◽

Cited By ~ 1

Author(s):

Muyun Peng ◽

Yuancai Xie ◽

Xiaohua Li ◽

Youhui Qian ◽

Xiaonian Tu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Cancer Detection ◽

Deep Sequencing ◽

Lung Diseases ◽

Early Cancer ◽

Lung Nodule ◽

Gene Mutations ◽

Tumour Tissue ◽

Early Cancer Diagnosis

BackgroundEarly detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumour (ct) DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery.MethodsThe multicentre clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white cell count genomic DNA (gDNA) and tumour tissue gDNA of each patient were analysed by ultra-deep sequencing to an average of 35 000× of the coding regions of 65 lung cancer-related genes.ResultsThe cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients are at stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%. When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for stages I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harboured mutations in the patients with lung cancer with the largest number found in TP53 (30% plasma and 62% tumour tissue samples) and EGFR (20% and 40%, respectively).ConclusionPlasma ctDNA was analysed in lung nodule assessment and early cancer detection, while an algorithm combining clinical information enhanced the test performance.Trial registration numberNCT03081741.

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A Clinocopathological Study of Lung Cancer in Patients with Non-Idiopathic Pulmonary Fibrosis (IPF) Diffuse Parenchymal Lung Diseases

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3367 ◽

2019 ◽

Author(s):

S. Fedyna ◽

W. Bulman ◽

C. Shu ◽

A. Saqi ◽

J. Sonett ◽

...

Keyword(s):

Lung Cancer ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Diseases ◽

Diffuse Parenchymal Lung Diseases ◽

Parenchymal Lung

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Hallmarks of the ageing lung

European Respiratory Journal ◽

10.1183/09031936.00186914 ◽

2015 ◽

Vol 45 (3) ◽

pp. 807-827 ◽

Cited By ~ 114

Author(s):

Silke Meiners ◽

Oliver Eickelberg ◽

Melanie Königshoff

Keyword(s):

Lung Cancer ◽

Chronic Obstructive Pulmonary Disease ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Pulmonary Disease ◽

Lung Diseases ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Specific Effects ◽

Chronic Lung Diseases

Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, “dysregulation of the extracellular matrix”, which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases.

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CADM1 and SPC25 gene mutations in lung cancer patients with idiopathic pulmonary fibrosis

JTO Clinical and Research Reports ◽

10.1016/j.jtocrr.2021.100232 ◽

2021 ◽

pp. 100232

Author(s):

Aya Fukuizumi ◽

Rintaro Noro ◽

Masahiro Seike ◽

Akihiko Miyanaga ◽

Yuji Minegishi ◽

...

Keyword(s):

Lung Cancer ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Cancer Patients ◽

Gene Mutations ◽

Lung Cancer Patients

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Investigation of telomere related gene mutations in idiopathic pulmonary fibrosis

Molecular Biology Reports ◽

10.1007/s11033-020-05861-1 ◽

2020 ◽

Vol 47 (10) ◽

pp. 7851-7860

Author(s):

Halime Yildirim ◽

Pinar Yildiz ◽

Ender Coskunpinar

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Gene Mutations ◽

Related Gene

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Mutations Associated with No Durable Clinical Benefit to Immune Checkpoint Blockade in Non-S-Cell Lung Cancer

Cancers ◽

10.3390/cancers13061397 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1397

Author(s):

Guangsheng Zhu ◽

Dian Ren ◽

Xi Lei ◽

Ruifeng Shi ◽

Shuai Zhu ◽

...

Keyword(s):

Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Clinical Benefit ◽

Gene Mutations ◽

Predictive Biomarker ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Related Gene ◽

Nsclc Patients

(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.

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The Frequency of Epidermal Growth Factor Receptor (EGFR) Mutation in Patients with Lung Cancer Referred to the Lung Diseases Hospital; A Cross Sectional Study

10.21203/rs.3.rs-452912/v1 ◽

2021 ◽

Author(s):

Sotoudeh Mohammadi ◽

Mitra rezaei ◽

Fatemeh Shojaeian ◽

Mihan Pouabdollah ◽

Leila Mohammadi Ziazi ◽

...

Keyword(s):

Lung Cancer ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Lung Diseases ◽

Gene Mutations ◽

Advanced Lung Cancer ◽

Cross Sectional ◽

Egfr Gene ◽

Epidermal Growth ◽

Iranian Patients

Abstract Background Various studies showed the usage of epidermal growth factor receptors (EGFRs) gene mutations in the therapeutic plan of patients with advanced lung cancer. This study aimed to investigate the frequency and types of EGFR gene mutations among Iranian patients with lung cancer referred to a specialized lung diseases hospital from 2014 to 2019. Results The study was included 570 individuals, with an average age of 58.74 years old, of which 51.6% were men and 48.4% were women. Gene mutations were present in 113 of the 570 (19.8%) participants. There was deletion, replacement, and deletion and replacement in 65 (57%), 48 (42.1%), and (0.9%) cases, respectively. The mutation was significantly higher among women (P = 0.001); in detail, deletion was higher among female participants, although the replacement mutation was the same in male and female groups. There were no significant differences in mutation among different age groups (P = 0.05). Conclusion EGFR gene mutations, associated with lung cancer and could help patients' therapeutic plan, had the frequency of about 19.8% among Iranian patients with lung cancer.

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