PIK3CA mutations are distinctive genetic features in non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD): A comprehensive mutational analysis from multi-institutional cohort.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20060-e20060
Author(s):  
Kenji Sawa ◽  
Tomoya Kawaguchi ◽  
Yasuhiro Koh ◽  
Satoshi Kambayashi ◽  
Kazuhisa Asai ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Early Stage ◽  
University Hospital ◽  
Multivariate Logistic Regression Model ◽  
Base Substitution ◽  
Chronic Obstructive ◽  
Pathological Stage ◽  
Pik3ca Mutations ◽  
Genetic Features ◽  
Nsclc Patients

e20060 Background: A mutual developmental mechanism has been proposed between NSCLC and COPD; however, the association is not fully understood. We previously reported that the mutations in PI3K/AKT/mTOR pathway and NFE2L2 were frequently observed and co-existed in NSCLC patients with COPD (Kawaguchi T, J Clin Oncol 34, 2016 [suppl; abstr 8526]). To further validate this finding, a new cohort was added and merged into the original cohort’s study. Methods: A total of 197 surgical specimens of early stage NSCLC including 90 newly added from Osaka City University hospital were collected between 2010 and 2013. Extracted DNAs were deep-sequenced using NGS technologies for somatic mutations in 72 cancer-associated genes for a molecular profiling in NSCLC patients with COPD. We defined COPD as presence of FEV1/FEV < 0.7 and classified the severity based on the Global Initiative for Chronic Obstructive Lung Disease. Results: The COPD group (N = 77) including 56 mild, 21 moderate/severe diseases, had 58 squamous cell carcinoma (SQ) and 19 adenocarcinoma (AD), with 70 smokers. The non-COPD group (N = 120) had 53 SQ, 64 AD and three others, with 78 smokers. The frequency of PIK3CA mutations was higher in COPD (10.4 %) than non-COPD (1.7 %), while in AD KRAS mutations were more frequent in COPD (21.1%) than non-COPD (9.4%). Notably, the frequency of PIK3CA mutations increased parallel to the COPD severity (p < 0.001). Meanwhile, NFE2L2 mutations were observed only in SQ, and no difference in the frequency was observed between the two groups (17.2% vs. 17.0%) unlike our previous analysis. In the multivariate logistic regression model, significantly more PIK3CA mutations were observed in the presence of COPD (Odds ratio = 5.47, 95%CI: 1.04-28.85, p = 0.045) with consideration of age, smoking dose, histology and pathological stage. The most frequent base substitution pattern in PIK3CA mutations was C > T change, suggesting the association with APOBEC-mediated mutagenesis. Conclusions: PIK3CA mutations are distinctive genetic features in NSCLC with COPD, regardless of age, smoking dose, histology and pathological stage.

scholarly journals The Ability of Metabolomics to Discriminate Non-Small-Cell Lung Cancer Subtypes Depends on the Stage of the Disease and the Type of Material Studied

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3314
Author(s):  
Tomasz Kowalczyk ◽  
Joanna Kisluk ◽  
Karolina Pietrowska ◽  
Joanna Godzien ◽  
Miroslaw Kozlowski ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Early Stage ◽  
Chronic Obstructive ◽  
Liquid Chromatography Mass Spectrometry ◽  
Obstructive Pulmonary Disease ◽  
Cell Lung Carcinoma ◽  
Cancer Subtypes ◽  
Inflammatory State ◽  
Nsclc Patients

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.

Mutational landscape with a focus on KRAS mutations in non-small lung cancer in Taiwan.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20513-e20513
Author(s):  
Nguyet Tran ◽  
Joseph D. Bonner ◽  
Wei-Ju Chen ◽  
Fang-Wei Lin ◽  
Peter J. Gruber ◽  
...  
Keyword(s):  
Lung Cancer ◽  
General Hospital ◽  
Mutational Analysis ◽  
Stage Iv ◽  
University Hospital ◽  
Egfr Mutations ◽  
Kras Mutations ◽  
Mutational Landscape ◽  
Nsclc Patients ◽  
Medical University

e20513 Background: Lung cancer is the leading cause of cancer death in Taiwan. The poor prognosis of lung cancer patients with advanced disease and recent development of precision medicine motivates the investigation of molecular targets. The purpose of the study is to estimate the prevalence of KRAS gene mutations and 15 other gene targets among non-small cell lung cancer (NSCLC) patients in Taiwan. Methods: This retrospective study included 933 NSCLC patients diagnosed between January 1992 and July 2018 at six medical centers in Taiwan, including Taichung Veteran’s General Hospital, Chung San Medical University Hospital, China Medical University Hospital, Kaohsiung Veteran’s General Hospital, Tri-Service General Hospital and National Taiwan University Hospital. Patients ≥18 years, had primary histologically confirmed NSCLC diagnosis at time before any treatment, and availability of archival tumor tissue with >30% tumor cellularity. Mutational Analysis: The Formalin-Fixed Paraffin-Embedded (FFPE) tumor blocks were analyzed for the prevalence of somatic mutations. The entire coding sequence of 16 genes was analyzed by next generation sequencing of macrodissected DNA from FFPE recut slides at a depth of greater than 300x and interrogated for somatic pathogenic variants. RNA was not available; hence this limits sensitivity to detect fusions. Results: The mean age at diagnosis was 62 years, 498/933 (53%) were women, 411/843 (49%) were smokers or former smokers, and 829/933 (89%) of adenocarcinoma histopathology. Stage was available for 723 patients with a distribution of 328/723 (45%) Stage I, 120/723 (17%) Stage II, 210/723 (29%) Stage III, and 65/723 (9%) Stage IV. EGFR mutations were identified in 327/933 (35.1%) and TP53 mutations in 179/933 (19.2%). KRAS mutations were identified in 72/933 (7.7%) patients, with KRAS G12C mutations observed in 23/933 (2.5%), KRAS G12D in 16/933 (1.7%), and KRAS G12V in 14/933 (1.5%) (Table). In addition, co-occurring mutations with KRAS were observed and are highlighted, including 14 TP53, 4 PIK3CA, 2 EGFR, 2 CTNNB1, 1 STK11, 1 BRAF and 1 PTEN. Conclusions: EGFR and TP53 were the most frequent mutations identified among all stage NSCLC in Taiwanese populations, followed by KRAS. KRAS G12C and KRAS G12D, the two most frequent KRAS mutations, were identified in 32% and 22% of the KRAS-mutant tumors. Although the prevalence of any KRAS mutation or KRAS G12C mutation is lower than typically seen in Western countries, it is similar to observations among Asian populations. These findings broaden the understanding of the mutational landscape of NSCLC patients in Taiwan to inform development of new therapeutic approaches. [Table: see text]

scholarly journals Human granulocytic anaplasmosis in a Single University Hospital in the Republic of Korea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Da Young Kim ◽  
Jun-Won Seo ◽  
Na Ra Yun ◽  
Choon-Mee Kim ◽  
Dong-Min Kim
Keyword(s):  
South Korea ◽  
Clinical Characteristics ◽  
Early Stage ◽  
University Hospital ◽  
Human Granulocytic Anaplasmosis ◽  
Granulocytic Anaplasmosis ◽  
Genetic Features ◽  
The Republic ◽  
Low Sensitivity ◽  
Time Of Admission

AbstractTo date, only a few studies have analyzed the clinical characteristics and genetic features of human granulocytic anaplasmosis (HGA) in South Korea. Thus, in this study, we investigated the clinical characteristics of HGA and methods used for clinical diagnosis. The clinical characteristics of patients with HGA were studied retrospectively. We reviewed the medical charts of 21 confirmed patients with HGA admitted to the Chosun University Hospital, located in Gwangju, South Korea. Twenty-one HGA patients visited the hospital 2–30 days (median 7 days) after the onset of symptoms. Fourteen patients (66.7%) had fever, which was alleviated 2 h (range 0–12.75 h) after starting treatment with doxycycline. Of the 18 patients who underwent peripheral blood (PB) smear test, only one (5.6%) had morulae. Additionally, only 4/17 patients (23.5%) had morulae in the PB smear reconducted after the confirmation of anaplasmosis. All 21 patients recovered without significant complications. As per results of the blood tests conducted at the time of admission, 7/21 (33.3%) and 5/21 (23.8%) patients showed at least 1:16 and 1:80 of IgM and IgG titers, respectively. Most HGA patients in Korea recovered without significant complications. The indirect immunofluorescence antibody diagnosis or morulae identification for HGA in this study had low sensitivity in the early stage of the disease.

PD-0418: Dose on cardiac (sub)structures as predictor for OS in early stage NSCLC patients treated with SBRT

2020 ◽  
Vol 152 ◽  
pp. S226-S227
Author(s):  
M. Duijm ◽  
D. Pezzulla ◽  
W. Schillemans ◽  
J. Nuyttens
Keyword(s):  
Early Stage ◽  
Early Stage Nsclc ◽  
Nsclc Patients

scholarly journals Contagion Management at the Méditerranée Infection University Hospital Institute

2021 ◽  
Vol 10 (12) ◽  
pp. 2627
Author(s):  
Pierre-Edouard Fournier ◽  
Sophie Edouard ◽  
Nathalie Wurtz ◽  
Justine Raclot ◽  
Marion Bechet ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Early Diagnosis ◽  
Personal Protective Equipment ◽  
Early Stage ◽  
Point Of Care ◽  
University Hospital ◽  
Protective Equipment ◽  
Monitoring Point ◽  
Epidemiological Monitoring ◽  
Wide Range

The Méditerranée Infection University Hospital Institute (IHU) is located in a recent building, which includes experts on a wide range of infectious disease. The IHU strategy is to develop innovative tools, including epidemiological monitoring, point-of-care laboratories, and the ability to mass screen the population. In this study, we review the strategy and guidelines proposed by the IHU and its application to the COVID-19 pandemic and summarise the various challenges it raises. Early diagnosis enables contagious patients to be isolated and treatment to be initiated at an early stage to reduce the microbial load and contagiousness. In the context of the COVID-19 pandemic, we had to deal with a shortage of personal protective equipment and reagents and a massive influx of patients. Between 27 January 2020 and 5 January 2021, 434,925 nasopharyngeal samples were tested for the presence of SARS-CoV-2. Of them, 12,055 patients with COVID-19 were followed up in our out-patient clinic, and 1888 patients were hospitalised in the Institute. By constantly adapting our strategy to the ongoing situation, the IHU has succeeded in expanding and upgrading its equipment and improving circuits and flows to better manage infected patients.

scholarly journals Serum surfactant protein D in COVID-19 is elevated and correlated with disease severity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ming Tong ◽  
Ying Xiong ◽  
Chen Zhu ◽  
Hong Xu ◽  
Qing Zheng ◽  
...  
Keyword(s):  
Acute Phase ◽  
Early Stage ◽  
Recovery Period ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Mean Value ◽  
Multivariate Logistic Regression Model ◽  
Surfactant Protein D ◽  
Multivariate Logistic Regression ◽  
Roc Curve Analysis

Abstract Background The serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated. Methods We performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People’s Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed. Results In the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, P<0.001), while the serum levels of SP-D in the recovery period were decreased dramatically than that in the acute phase (mean value ± SD, 129.5 ± 51.7 vs 292.9 ± 130.7 ng/ml, P<0.001), and so were for the stratified patients. The chest CT imaging scores were considerably higher in the severe group compared with those in the mild group (median value, 10.0 vs 9.0, P = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, P<0.001), and so were for the stratified patients. ROC curve analysis revealed that areas under the curve of lymphocyte counts (LYM), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and SP-D for severe COVID-19 were 0.719, 0.833, 0.817, 0.837, and 0.922, respectively. Correlation analysis showed that the SP-D levels were negatively correlated with LYM (r = − 0.320, P = 0.047), while positively correlated with CRP (r = 0.658, P<0.001), IL-6 (r = 0.471, P = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, P<0.001), chest CT imaging score on admission (r = 0.695, P<0.001) and length of stay (r = 0.420, P = 0.008). Multivariate logistic regression model analysis showed that age (P = 0.041, OR = 1.093) and SP-D (P = 0.008, OR = 1.018) were risk factors for severe COVID-19. Conclusions Elevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.

scholarly journals A population-based analysis of spirometry use and the prevalence of chronic obstructive pulmonary disease in lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sophie Corriveau ◽  
Gregory R. Pond ◽  
Grace H. Tang ◽  
John R. Goffin
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Early Stage ◽  
Advanced Lung Cancer ◽  
Public Healthcare ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Early Stage Disease ◽  
Morbidity Score

Abstract Background Chronic obstructive pulmonary disease (COPD) and lung cancer are associated diseases. COPD is underdiagnosed and thus undertreated, but there is limited data on COPD diagnosis in the setting of lung cancer. We assessed the diagnosis of COPD with lung cancer in a large public healthcare system. Methods Anonymous administrative data was acquired from ICES, which links demographics, hospital records, physician billing, and cancer registry data in Ontario, Canada. Individuals age 35 or older with COPD were identified through a validated, ICES-derived cohort and spirometry use was derived from physician billings. Statistical comparisons were made using Wilcoxon rank sum, Cochran-Armitage, and chi-square tests. Results From 2002 to 2014, 756,786 individuals were diagnosed with COPD, with a 2014 prevalence of 9.3%. Of these, 51.9% never underwent spirometry. During the same period, 105,304 individuals were diagnosed with lung cancer, among whom COPD was previously diagnosed in 34.9%. Having COPD prior to lung cancer was associated with lower income, a rural dwelling, a lower Charlson morbidity score, and less frequent stage IV disease (48 vs 54%, p < 0.001). Spirometry was more commonly undertaken in early stage disease (90.6% in stage I-II vs. 54.4% in stage III-IV). Conclusion Over a third of individuals with lung cancer had a prior diagnosis of COPD. Among individuals with advanced lung cancer, greater use of spirometry and diagnosis of COPD may help to mitigate respiratory symptoms.

scholarly journals Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Early Stage Nsclc ◽  
Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

scholarly journals Implementation of a Targeted Screening Program to Detect Airflow Obstruction Suggestive of Chronic Obstructive Pulmonary Disease within a Presurgical Screening Clinic

2015 ◽  
Vol 22 (4) ◽  
pp. 209-214 ◽  
Author(s):  
Chantal Robitaille ◽  
Esther Dajczman ◽  
Andrew M Hirsch ◽  
David Small ◽  
Pierre Ernst ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Screening Program ◽  
Tertiary Care ◽  
Airflow Obstruction ◽  
University Hospital ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Targeted Screening ◽  
History Of

BACKGROUND: Targeted spirometry screening for chronic obstructive pulmonary disease (COPD) has been studied in primary care and community settings. Limitations regarding availability and quality of testing remain. A targeted spirometry screening program was implemented within a presurgical screening (PSS) clinic to detect undiagnosed airways disease and identify patients with COPD/asthma in need of treatment optimization.OBJECTIVE: The present quality assurance study evaluated airflow obstruction detection rates and examined characteristics of patients identified through the targeted screening program.METHODS: The targeted spirometry screening program was implemented within the PSS clinic of a tertiary care university hospital. Current or ex-smokers with respiratory symptoms and patients with a history of COPD or asthma underwent prebronchodilator spirometry. History of airways disease and smoking status were obtained during the PSS assessment and confirmed through chart reviews.RESULTS: After exclusions, the study sample included 449 current or ex-smokers. Abnormal spirometry results were found in 184 (41%) patients: 73 (16%) had mild, 93 (21%) had moderate and 18 (4%) had severe or very severe airflow obstruction. One hundred eighteen (26%) new cases of airflow obstruction suggestive of COPD were detected. One-half of these new cases had moderate or severe airflow obstruction. Only 34% of patients with abnormal spirometry results had reported a previous diagnosis of COPD. More than one-half of patients with abnormal spirometry results were current smokers.CONCLUSIONS: Undiagnosed airflow obstruction was detected in a significant number of smokers and ex-smokers through a targeted screening program within a PSS clinic. These patients can be referred for early intervention and secondary preventive strategies.

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