Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma.

Background: Pleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.

Thoracic radiation in combination with erlotinib-results from a phase 2 randomized trial.

Background: Radiotherapy (RT) can be used to reduce symptoms and maintain open airways for patients with non-small cell lung cancer when systemic treatment is not sufficient. For some patients, tumor control is not achieved due to radioresistance. Concurrent inhibition of epidermal growth factor receptors has been proposed as a strategy to overcome radioresistance but may increase toxicity.

UV1 telomerase vaccine with ipilimumab and nivolumab as second line treatment for pleural mesothelioma - A phase II randomised trial.

Purpose: The NIPU-trial investigates the effect of adding the telomerase vaccine UV1 to treatment with ipilimumab and nivolumab for patients with pleural mesothelioma (PM).

Methods: In this phase 2 open-label trial, patients with PM progressing after first-line chemotherapy were randomised to receive ipilimumab and nivolumab alone (arm B) or combined with UV1 (arm A). The primary endpoint was progression-free survival (PFS) as determined by BICR.

Atezolizumab and stereotactic body radiotherapy in patients with advanced non-small cell lung cancer: safety, clinical activity and ctDNA responses-the ComIT-1 trial.

The introduction of immune checkpoint inhibitors has transformed the treatment landscape of metastatic non-small cell lung cancer. However, challenges remain to increase the fraction of patients achieving durable clinical responses to these drugs and to help monitor the treatment effect. In this phase II trial, we investigated the toxicity, systemic responses and circulating tumour DNA responses in patients (n = 21) with advanced non-small-cell lung cancer treated with atezolizumab and stereotactic body radiotherapy in the second or later line.

Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC.

The interaction between DNA methylation of tripartite motif containing 27 (cg05293407 ) and smoking has previously been identified to reveal histologically heterogeneous effects of TRIM27 DNA methylation on early-stage non-small-cell lung cancer (NSCLC) survival. However, to understand the complex mechanisms underlying NSCLC progression, we searched three-way interactions. A two-phase study was adopted to identify three-way interactions in the form of pack-year of smoking (number of cigarettes smoked per day × number of years smoked) × cg05293407  × epigenome-wide DNA methylation CpG probe.

Whole genome copy number analyses reveal a highly aberrant genome in TP53 mutant lung adenocarcinoma tumors.

Background: Genetic alterations are common in non-small cell lung cancer (NSCLC), and DNA mutations and translocations are targets for therapy. Copy number aberrations occur frequently in NSCLC tumors and may influence gene expression and further alter signaling pathways. In this study we aimed to characterize the genomic architecture of NSCLC tumors and to identify genomic differences between tumors stratified by histology and mutation status.

Improved adaptive radiotherapy to adjust for anatomical alterations during curative treatment for locally advanced lung cancer.

Anatomical changes during chemoradiation for lung cancer may decrease dose to the target or increase dose to organs at risk. To assess our ability to identify clinically significant anatomical alterations, we followed 67 lung cancer patients by daily cone-beam CT scans to ensure correct patient positioning and observe anatomical alterations. We also re-calculated the original dose distribution on a planned control CT scan obtained halfway during the treatment course to identify anatomical changes that potentially affected doses to the target or organs at risk.

NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for.

Epigenetic-smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early-stage NSCLC patients.

Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas.

Epigenome-wide gene-age interaction analysis reveals reversed effects of DNA methylation on survival between young and elderly early-stage NSCLC patients.

DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts.

Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma.

Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase.

SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic-smoking interaction analysis.

Smoking cessation prolongs survival and decreases mortality of patients with non-small-cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed.

EMT network-based feature selection improves prognosis prediction in lung adenocarcinoma.

Various feature selection algorithms have been proposed to identify cancer prognostic biomarkers. In recent years, however, their reproducibility is criticized. The performance of feature selection algorithms is shown to be affected by the datasets, underlying networks and evaluation metrics.

EGLN2 DNA methylation and expression interact with HIF1A to affect survival of early-stage NSCLC.

Hypoxia occurs frequently in human cancers and promotes stabilization and activation of hypoxia inducible factor (HIF). HIF-1α is specific for the hypoxia response, and its degradation mediated by three enzymes EGLN1, EGLN2 and EGLN3. Although EGLNs expression has been found to be related to prognosis of many cancers, few studies examined DNA methylation in EGLNs and its relationship to prognosis of early-stage non-small cell lung cancer (NSCLC).

DNA Methylation of : A Biomarker for Survival of Early-Stage Non-Small Cell Lung Cancer Patients.

Background: Previous studies support a tumor-suppressor role for across various types of cancers. We aimed to investigate the association between DNA methylation of 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.

A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer.

B-cell translocation gene 2 (BTG2) is a tumour suppressor protein known to be downregulated in several types of cancer. In this study, we investigated a potential role for BTG2 in early-stage non-small cell lung cancer (NSCLC) survival. We analysed BTG2 methylation data from 1230 early-stage NSCLC patients from five international cohorts, as well as gene expression data from 3038 lung cancer cases from multiple cohorts.

Epigenetic modifications in lysine demethylases associate with survival of early-stage NSCLC.

Background: lysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations in genes and their roles in lung cancer survival.

Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts.

A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer.

Introduction: Circulating microRNAs are promising biomarkers for diagnosis, predication and prognostication of diseases. Lung cancer is the cancer disease accountable for most cancer deaths, largely due to being diagnosed at late stages. Therefore, diagnosing lung cancer patients at an early stage is crucial for improving the outcome.

The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma--differences in histological subtypes.

Background: Extensive research has increased our understanding of the molecular alterations needed for non-small cell lung cancer (NSCLC) development. Deregulation of a pathway including MYCN, HMGA2 and CDKN2A, with the participation of DICER1, is of importance in several solid tumours, and may also be of significance in the pathogenesis of NSCLC.

Methods: Gene expression of MYCN, HMGA2, CDKN2A and DICER1 were investigated with RT-qPCR in surgically resected NSCLC tumour tissue from 175 patients.

Genome-wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR, KRAS and TP53 mutation status, gene expression and prognosis.

Background: DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed.

Results: We determined whole-genome DNA methylation profiles of 164 fresh frozen lung adenocarcinoma samples and 19 samples of matched normal lung tissue using the Illumina Infinium 450K array.

Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas.

The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post-transcriptional level.