Project description:Dysregulated expression of DEPDC1B (DEP domain-containing protein 1B) has been reported to be implicated in various types of malignancies. However, its functional implication as well as the underlying molecular mechanism in lung adenocarcinoma (LUAD) remains elusive. In this study, the role and clinical significance of DEPDC1B in LUAD has been systematically investigated. Our results first showed that DEPDC1B is significantly upregulated in various types of cancers including LUAD, and high DEPDC1B expression is remarkably associated with poor survival in LUAD patients. Functional study demonstrated that DEPDC1B knockdown inhibited cell growth, cell cycle progression, colony formation, cell migration and motility. Furthermore, xenograft nude mouse model experiments showed that DEPDC1B silencing resulted in significant inhibition of tumor growth in vivo. Detailed mechanistic experiments revealed that DEPDC1B knockdown caused down-regulation of various downstream genes including NID1, FN1 and EGFR, and inactivation of multiple critical pathways including ERK and PI3K-AKT pathways.
Project description:To explore malignant phenotype related genes in Panc-1-CTC, we performed gene expression array analysis with Panc-1-CTC and Panc-1-Parent (Panc-1-P). As a result, TGFBI upregulation emerged as highly malignant feature for pancreatic ductal adenocarcinoma. Identification of malignant phenotype related genes in pancreatic ductal adenocarcinoma
Project description:Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF. Keywords: array comparitive genomic hybridization, bronchioloalveolar carcinoma, non-small-cell lung carcinoma, prognostic markers Array comparitive genomic hybridization analysis of 29 Lung Adenocarcinomas with Bronchioalveolar Features.
Project description:Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF. Keywords: array comparitive genomic hybridization, bronchioloalveolar carcinoma, non-small-cell lung carcinoma, prognostic markers
Project description:Aberrant differentiation, driven by activation of normally silent tissue-specific genes, results in a switch of cell identity and often leads to cancer progression. The underlying genetic and epigenetic events are largely unexplored. Here, we report ectopic activation of the hepatobiliary-, intestinal- and neural-specific gene one cut homeobox 2 (ONECUT2) in various subtypes of lung cancer. ONECUT2 expression was associated with poor prognosis of RAS-driven lung adenocarcinoma. ONECUT2 overexpression promoted the malignant growth and invasion of A549 lung cancer cells in vitro, as well as xenograft tumorigenesis and bone metastases of these cells in vivo. Integrative transcriptomics and epigenomics analyses suggested that ONECUT2 promoted the trans-differentiation of lung cancer cells by preferentially targeting and regulating the activity of bivalent chromatin domains through modulating Polycomb Repressive Complex 2 (PRC2) occupancy. Our findings demonstrate that ONECUT2 is a lineage-specific and context-dependent oncogene in lung adenocarcinoma and suggest that ONECUT2 is a potential therapeutic target for these tumors.
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most hypoxic, lethal, and treatment resistant cancers. Due to its desmoplastic and hypoxic nature along with the abundance of myeloid cell infiltration and scare T cell infiltration, PDAC is considered a cold tumor. Using MiaPaCA-2 as a PDAC spheroid model with hypoxic core grown in serum-free defined media and immune cell infiltration, we assessed the modulation of PDAC secretome and characterized immunomodulatory factors secreted.
Project description:Here, we have reported the plasma proteomes of 6 malignant melanoma (MM) and 6 lung adenocarcinoma (LUAD) patients, generated using HiRIEF pre-fractionation and tandem mass tags (TMT)-based peptide quantification. We have detected traditional plasma marker proteins, as well as many LUAD and MM related proteins in the cancer plasma. Our advanced proteomics workflow exhibits high proteome coverage for both plasma and plasma derived extracellular vesicles (pEVs), providing the ability to detect potential disease-specific markers in pEVs enriched from clinical plasma samples.
Project description:We profiled the exosomal circRNA in lung adenocarcinoma-associated malignant (LA-MPE) and tuberculous (TPE) pleural effusion samples by circRNA microarray to determine the potential functions and diagnostic value of the differential expressed circRNAs (DECs)