Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma.

Background: The current classification of human lung adenocarcinoma defines five different histological growth patterns within the group of conventional invasive adenocarcinomas. The five growth patterns are characterised by their typical architecture, but also by variable tumor biological behaviour.

Aims: The aim of this study was to identify specific gene signatures of the five adenocarcinoma growth patterns defined by the joint IASLC/ATS/ERS working group.

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer.

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors.

BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence.

Prostate cancer is driven by a combination of genetic and/or epigenetic alterations. Epigenetic alterations are frequently observed in all human cancers, yet how aberrant epigenetic signatures are established is poorly understood. Here we show that the gene encoding BAZ2A (TIP5), a factor previously implicated in epigenetic rRNA gene silencing, is overexpressed in prostate cancer and is paradoxically involved in maintaining prostate cancer cell growth, a feature specific to cancer cells.

Activation of AMP-activated protein kinase sensitizes lung cancer cells and H1299 xenografts to erlotinib.

Objectives: The therapeutic scheme for non-small cell lung cancer (NSCLC) patients can be improved if adapted to the individual response. For example, 60-70% of adenocarcinoma patients show response to EGFR-tyrosine kinase inhibitors in the presence of mutated EGFR. We searched for additional target molecules involved in the action of the EGFR-tyrosine kinase inhibitor erlotinib in the absence of EGFR mutations, which might be suitable for combinatorial therapy approaches.

ERG induces epigenetic activation of Tudor domain-containing protein 1 (TDRD1) in ERG rearrangement-positive prostate cancer.

Background: Overexpression of ERG transcription factor due to genomic ERG-rearrangements defines a separate molecular subtype of prostate tumors. One of the consequences of ERG accumulation is modulation of the cell's gene expression profile. Tudor domain-containing protein 1 gene (TDRD1) was reported to be differentially expressed between TMPRSS2:ERG-negative and TMPRSS2:ERG-positive prostate cancer.

Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer.

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms.

Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients.

The outcome of resectable non-small cell lung cancer (NSCLC) is critically determined by metastatic spread: About 30-50% of early-stage NSCLC patients encounter tumour recurrence within 5 years after surgery. A biomarker-driven stratification of early-stage lung cancer with a high risk of recurrence may improve therapy management and patient care. The aim of this study was to identify microRNAs (miRNAs) in serum of patients associated with early relapse in pulmonary adenocarcinoma.

Mesenchymal stem cells in non-small cell lung cancer--different from others? Insights from comparative molecular and functional analyses.

Background: Cancer-associated fibroblasts (CAF) play a vital role in lung cancer initiation and progression. Although mesenchymal stem cells (MSC) are considered progenitor cells of fibroblasts and show cancer modulating abilities themselves, analyses on their presence and properties in lung cancer are lacking so far.

Methods: We performed a comparative molecular and functional analysis of MSC derived from non-small cell lung cancer (NSCLC) and corresponding normal lung tissue (NLT) of a total of 15 patients.

Lung Cancer Gene Signatures and Clinical Perspectives.

Microarrays have been used for more than two decades in preclinical research. The tumor transcriptional profiles were analyzed to select cancer-associated genes for in-deep functional characterization, to stratify tumor subgroups according to the histopathology or diverse clinical courses, and to assess biological and cellular functions behind these gene sets. In lung cancer-the main type of cancer causing mortality worldwide-biomarker research focuses on different objectives: the early diagnosis of curable tumor diseases, the stratification of patients with prognostic unfavorable operable tumors to assess the need for further therapy regimens, or the selection of patients for the most efficient therapies at early and late stages.

The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer.

Loss of cell cycle control is a prerequisite for cancer onset and progression. In prostate cancer, increased activity of cell cycle genes has been associated with prognostic parameters such as biochemical relapse and survival. The identification of novel oncogenic and druggable targets in patient subgroups with poor prognosis may help to develop targeted therapy approaches.

Genome-wide DNA methylation events in TMPRSS2-ERG fusion-negative prostate cancers implicate an EZH2-dependent mechanism with miR-26a hypermethylation.

Unlabelled: Prostate cancer is the second most common cancer among men worldwide. Alterations in the DNA methylation pattern can be one of the leading causes for prostate cancer formation. This study is the first high-throughput sequencing study investigating genome-wide DNA methylation patterns in a large cohort of 51 tumor and 53 benign prostate samples using methylated DNA immunoprecipitation sequencing.

microRNA biomarkers in body fluids of prostate cancer patients.

The abundance of miRNAs - small non-coding RNAs involved in posttranscriptional regulation of gene expression - in tissues and body fluids of cancer patients hold great promise to identify specific biomarkers, which may be useful for early diagnosis as well as to predict the clinical outcome and treatment response. For the extraction and quantification of miRNAs from cells and tissues, present technologies for transcriptome analyses like microarrays, quantitative real-time PCR or next generation sequencing can be applied. However, the analyses of miRNAs in body fluids like serum or urine is still a challenge with respect to the nucleic acid recovery from very limited sources of biomaterial, normalization strategies and validation using independent technologies.

Early detection of lung cancer by molecular markers in endobronchial epithelial-lining fluid.

Introduction: Early detection of malignancies in the lung by less-invasive methods aims at achieving efficient intervention and subsequently a reduction of the high mortality rate. We investigated whether biomarker analysis in endobronchial epithelial-lining fluid (ELF) collected by bronchoscopic microsampling (BMS) may be useful for a definitive preoperative diagnosis.

Methods: ELF was collected from subsegmental bronchi close to the indeterminate pulmonary nodule, which was detected by computed tomography, and from the contralateral lung.

Peroxiredoxins 3 and 4 are overexpressed in prostate cancer tissue and affect the proliferation of prostate cancer cells in vitro.

The present study aimed to investigate the proteome profiling of surgically treated prostate cancers. Hereto, 2D-DIGE and mass spectrometry were performed for protein identification, and data validation for peroxiredoxin 3 and 4 (PRDX3 and PRDX4) was accomplished by reverse phase protein arrays (RPPA). The Formal Concept Analysis (FCA) method was applied to assess whether the TMPRSS2-ERG gene fusion could influence the degree of overexpression of PRDX3 and PRDX4 in prostate cancer.

Graph based fusion of miRNA and mRNA expression data improves clinical outcome prediction in prostate cancer.

Background: One of the main goals in cancer studies including high-throughput microRNA (miRNA) and mRNA data is to find and assess prognostic signatures capable of predicting clinical outcome. Both mRNA and miRNA expression changes in cancer diseases are described to reflect clinical characteristics like staging and prognosis. Furthermore, miRNA abundance can directly affect target transcripts and translation in tumor cells.

TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling.

Background: TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear.

Methods: We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.

Establishment and comparative characterization of novel squamous cell non-small cell lung cancer cell lines and their corresponding tumor tissue.

Background: Cell lines play an important role for studying tumor biology and novel therapeutic agents. Particularly in pulmonary squamous cell carcinoma (SCC) the availability of cell lines is limited and knowledge about their representativeness for corresponding tumor tissue is scanty.

Materials And Methods: We established three novel SCC cell lines from fresh tumor tissue of 28 donors, including 8 SCC.

Loss of aquaporin-4 expression and putative function in non-small cell lung cancer.

Background: Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs.

Methods: We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry.

Serum microRNAs as non-invasive biomarkers for cancer.

Human serum and other body fluids are rich resources for the identification of novel biomarkers, which can be measured in routine clinical diagnosis. microRNAs are small non-coding RNA molecules, which have an important function in regulating RNA stability and gene expression. The deregulation of microRNAs has been linked to cancer development and tumor progression.

Circulating miRNAs are correlated with tumor progression in prostate cancer.

Circulating miRNAs have recently been indicated as practicable and promising biomarkers for noninvasive diagnosis in various tumor entities. However, cell-free miRNAs have not been found to correlate with clinicopathological variables in epithelial carcinomas. To learn more about the potential clinical relevance of circulating miRNAs in prostate cancer, we screened 667 miRNAs in serum samples from patients with metastatic (n = 7) and localized prostate cancer (n = 14).

Classification across gene expression microarray studies.

Background: The increasing number of gene expression microarray studies represents an important resource in biomedical research. As a result, gene expression based diagnosis has entered clinical practice for patient stratification in breast cancer. However, the integration and combined analysis of microarray studies remains still a challenge.

Differential expression of apoptotic genes PDIA3 and MAP3K5 distinguishes between low- and high-risk prostate cancer.

Background: Despite recent progress in the identification of genetic and molecular alterations in prostate cancer, markers associated with tumor progression are scarce. Therefore precise diagnosis of patients and prognosis of the disease remain difficult. This study investigated novel molecular markers discriminating between low and highly aggressive types of prostate cancer.

Gene expression analysis of endobronchial epithelial lining fluid in the evaluation of indeterminate pulmonary nodules.

Objective: Making a definitive preoperative diagnosis in patients with indeterminate pulmonary nodules is still a challenge. Gene expression profiling may be a useful adjunctive diagnostic utility in this regard. We investigated the feasibility of bronchoscopic microsampling to collect endobronchial epithelial lining fluid to obtain RNA as a starting point for gene expression profiling.