Project description:Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking. Based on the hypothesis that smoking-specific miRNA differences in lung adenocarcinomas reflect distinct tumorigenic processes selected by different smoking and non-smoking environments, we investigated the contribution of miRNA disruption to lung tumor biology and patient outcome in the context of smoking status. Results: We discovered novel and distinct smoking-status-specific patterns of miRNA and miRNA-mediated gene networks, and identified miRNAs that were prognostically significant in a smoking-dependent manner. Conclusions: We conclude that miRNAs disrupted in a smoking-status-dependent manner affect distinct cellular pathways and differentially influence lung cancer patient prognosis in current, former and never smokers. Our findings may represent promising biologically relevant markers for lung cancer prognosis or therapeutic intervention. We applied a whole transcriptome sequencing based approach to interrogate miRNA levels in 94 patient-matched lung adenocarcinoma and non-malignant lung parenchymal tissue pairs from current [CS], former [FS] and never smokers [NS].
Project description:Using protein microarrays, derived from 642 His-tag proteins, we could distinguish sera from breast-nodule positive patients and healthy control individuals. Each Protein microarray was divided in to 4 sub-arrays. Each protein was spotted in duplicates in each sub-array. For evaluation 24 malignant, 16 benign breast cancer serum samples and 20 healthy control serum samples were used.
Project description:The proteomics analysis of circulating exosomes derived from cancer cells represents a promising approach to the elucidation of cell-cell communication and the discovery of putative biomarker candidates for cancer diagnosis and treatment. Nonetheless, the proteome of exosomes derived from cell lines with different metastatic capabilities still warrants further investigation. Here, we present a comprehensive quantitative proteomics investigation of exosomes isolated from im-mortalized mammary epithelial cells and matched tumor lines with different metastatic potential, in an attempt to discover exosome markers specific to breast cancer (BC) metastasis. A total of 2,135 unique proteins were quantified with a high confidence level from 20 isolated exosome samples, including 94 of the TOP 100 exosome markers archived by ExoCarta, e.g., CD9, HSPa8, and PDCD6IP. Moreover, 344 altered proteins were observed, among which several metastasis-specific markers, including CATW, MRS2, SDCB2, RTN4, and RAD23B, were also identified. Notably, the abundance of these metastasis-specific corresponds well with the overall survival of BC patients in clinical settings. Together, these data provide a valuable dataset for BC exosome proteomics in-vestigation and prominently facilitate the elucidation of the molecular mechanisms underlying primary tumor development and progression.
Project description:To explore ZNF555 function in non-malignant and malignant cells and characterize the ZNF555-associated phenotype, we generated several models modulating ZNF555 expression.
Project description:Analysis of 143 completely histologically-normal breast tissues resulted in the identification of a âÂÂmalignancy riskâ gene signature that may serve as a marker of subsequent risk of breast cancer development. Experiment Overall Design: RNA was extracted from microdissected frozen breast tissues for gene array analysis