Project description:Clinical FFPE tissue proteomic analyses were performed for early lung adenocarcinomas including adenocarcinoma in-situ (AIS), minimally invasive adenocarcinoma (MIA) and lepidic predominant invasive adenocarcinoma (LPA).
Project description:To determine the circRNA expression profile in early stage lung adenocarcinoma and matched non-tumor tissues, we used circRNA microArray analysis form Arraystar to examine the expression of circRNAs Lung adenocarcinoma, a form of NSCLC with high lethality at advanced stage, is becoming more popular in women, non- or never-smokers, and even young adult. However, there are no effective early diagnosis methods at present for patients to cure timely. Circular RNAs (circRNAs) as a special novel, stable, and conserved non-coding RNA in mammalian cells have been reported to be widely involved in the processes of cancer disease. Yet, it is still a puzzle which specific circRNAs are involved in the development of early stage lung adenocarcinoma. Here, tumour samples and paired adjacent normal tissues from 4 patients with early stage lung adenocarcinoma were selected for investigating the expression profile of circRNAs by using the high-throughput circRNA microarray. Bioinformatic analyses were conducted to screen those differentially expressed circRNAs. This work illustrates that clusters of circRNAs are aberrantly expressed in early stage lung adenocarcinoma, which might be able to provide potential targets for the early diagnosis of this disease and new genetic insights into lung cancer.
Project description:Lung adenocarcinoma is the most common histological subtype of lung cancer. Although early-stage LUAD (esLUAD) patients have much better prognosis than patients with advanced disease, among early stage patients treated primarily with surgery, some of early stage patients will develop metastasis with overall 5 year survival for stage 1 and 2 non-small cell lung cancer of 70% and 35%, respectively. Within lung adenocarcinoma, histology is heterogenous and associated with tumor invasion and clinical outcomes. Invasiveness is one of cancer hallmarks and is directly related with metastatic potential and clinical outcomes of the tumor. In this study, we characterize invasiveness mechanisms in esLUAD by analyzing gene expression of a novel cohort of 53 histologically heterogenous esLUAD samples.
Project description:The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing of samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could be used to categorize tumors into molecular subtypes within pathology-defined types of lesions. These subtypes were linked with the advanced radiology-defined type of lesions and corresponded to immune cell infiltration throughout the early progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.
Project description:To investigate the mechanism associated with cis-platin intrinsic resistance, we established a model of early drug-tolerant persister cells by exposing lung adenocarcinoma cell lines to the drug for 24 h. Then, we analyzed the transcriptome using RNA-seq from 4 different lung adenocarcinoma cell lines.
Project description:Purpose: Serum markers that enable diagnosis in the early stage of lung cancer have not been discovered. We have developed a LC-MRM-MS assay for the identification of potential early marker proteins for lung adenocarcinoma.
Experimental design: LC-MRM-MS assay was used for measuring the level of 35 candidate peptides in plasma from 102 lung adenocarcinoma patients (including n=50, 16, 24, and 12 in stage I, II, III, and IV, respectively.) and 84 healthy controls. Stable isotope labeled standard peptides were synthesized to accurately measure the amount of these proteins.
Results: Seven proteins were found to be able to distinguish stage I patients from controls. These proteins were combined in to a protein marker panel which improved the sensitivity to discriminate stage I patients from controls and resulted in a high classification performance with cross-validated area under the curve=0.76. Besides, we found that low expression of eukaryotic initiation factor 4A-I and high expression of lumican showed significantly poor prognosis in overall survival (p=0.012 and 0.0074, respectively), which may be used as prognostic biomarkers for lung cancer.
Conclusion and clinical relevance: Proteins highlighted here may be used for early detection of lung adenocarcinoma or therapeutics development after validation in a larger cohort.
Project description:Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis, with a 5-year survival rate of 100%. However, early invasive adenocarcinoma (EIA) often has a fatal outcome. In this study, we compared the expression profiles of AIS with those of EIA showing a fatal outcome, and screened the differentially expressed genes by cDNA microarray.