Correction: Methylation Markers of Early-Stage Non-Small Cell Lung Cancer.
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ABSTRACT:
SUBMITTER: Lokk K
PROVIDER: S-EPMC5249104 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Correction: Methylation Markers of Early-Stage Non-Small Cell Lung Cancer.
Lokk Kaie K Vooder Tõnu T Kolde Raivo R Välk Kristjan K Võsa Urmo U Roosipuu Retlav R Milani Lili L Fischer Krista K Koltsina Marina M Urgard Egon E Annilo Tarmo T Metspalu Andres A Tõnisson Neeme N
PloS one 20170120 1
[This corrects the article DOI: 10.1371/journal.pone.0039813.]. ...[more]
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Project description:We are investigating the molecular development of squamous cell lung carcinoma based upon analysis of global gene expression profiles representing progressive stages of cancer development, consisting of precancerous, carcinoma-in-situ, and invasive cancer. Keywords: global gene expression analysis, lung cancer development In this study, we have generated 13 SAGE libraries, consisting of five carcinoma-in-situ libraries, six early invasive squamous cell carcinoma libraries, and two reference libraries representing precancerous squamous development.
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Project description:Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice.
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Project description:IntroductionThe present study explores changes in pulmonary function, symptoms and radiological signs of pneumonitis after curatively intended stereotactic body radiation therapy (SBRT).MethodsAll inoperable, early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy (SBRT) from 2014-2017 were included in this single-centre study. They were followed regularly for 12 months after treatment. The patients were classified into three groups based on radiology and symptomatology: no radiation pneumonitis, asymptomatic and symptomatic radiation pneumonitis.ResultsForty-four patients with stage IA-IIB disease were treated with 45-56 Gy in 3-8 fractions. The median age was 75 years, 43% of the patients were female; 60% of the patients had a COPD in GOLD grade of 2-4, and 95.5% were active or former smokers. Symptomatic radiation pneumonitis occurred in 18% of the patients and asymptomatic pneumonitis as defined by radiology, in 39%. The mean of forced expiratory volume in 1 second (FEV1) and diffusion capacity for carbon monoxide (DLCO) decreases for all patients during the first years were higher than one would expect from physiologic ageing. FEV1 and DLCO in percent decrease 7-8% at 1-1.5 months in the symptomatic radiation pneumonitis group. CT scan findings consistent with radiation pneumonitis occurred after a median of 2.9 months in the symptomatic and 5.4 months in the asymptomatic radiation pneumonitis groups. In the group with symptomatic radiation pneumonitis, symptoms, as measured by the Clinical COPD questionnaire score, significantly increased at 3 and 6 months. Significant higher maximum doses to the critical lung volumes DC1000cm3 (1000 cm3 of lung receiving a given dose or less) and DC 1500cm3 (1500 cm3 of lung receiving a given dose or less) were observed in patients who developed radiation pneumonitis.ConclusionEarly decrease in measured FEV1 and DLCO occurred before imaging changes and symptoms and might indicate the development of symptomatic radiation pneumonitis. The dose to critical lung volumes of DC1000 cm3 and DC1500 cm3 may predict the risk for the development of symptomatic radiation pneumonitis.
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Project description:BACKGROUND:Previous studies support a tumor-suppressor role for LRRC3B across various types of cancers. We aimed to investigate the association between DNA methylation of LRRC3B and overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC). METHODS:This study included 1,230 patients with early-stage NSCLC. DNA was extracted from lung tumor tissues and DNA methylation was measured using Illumina Infinium HumanMethylation450 BeadChips. The association between DNA methylation and OS was first tested using Cox regression on a discovery cohort and then validated in an independent cohort. Next, the association between DNA methylation and gene expression was investigated in two independent cohorts. Finally, the association between gene expression and OS was investigated in three independent groups of patients. RESULTS:Three novel DNA methylation sites in LRRC3B were significantly associated with OS in two groups of patients. Patients with hypermethylation in the DNA methylation sites had significantly longer survival than the others in both the discovery cohort (HR, 0.62; P = 2.02 × 10-05) and validation cohort (HR, 0.55; P = 4.44 × 10-04). The three DNA methylation sites were significantly associated with LRRC3B expression, which was also associated with OS. CONCLUSIONS:Using clinical data from a large population, we illustrated the association between DNA methylation of LRRC3B and OS of early-stage NSCLC. IMPACT:We provide evidence of plausibility for building biomarkers on DNA methylation of LRRC3B for OS of early-stage NSCLC, thus filling a gap between previous in vitro studies and clinical applications.
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