calca-protein--human and Carcinoma--Non-Small-Cell-Lung

Topics: Aged; Area Under Curve; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Non-Small-Cell Lung; Female; Humans; Infections; Lung Neoplasms; Male; Predictive Value of Tests; Protein Precursors; Retrospective Studies; ROC Curve

Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood.. We determined the promoter methylation of 6 genes and PIK3CA amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with PIK3CA amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC).. Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of CALCA, CDH1, DAPK1, and EVX2 was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of RASSF1A methylation in ADC than SCC. In addition, PIK3CA amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with PIK3CA amplification.. Our data showed highly frequent promoter methylation and PIK3CA amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with PIK3CA amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway.

Topics: Antigens, CD; Apoptosis Regulatory Proteins; Cadherins; Calcitonin; Calcitonin Gene-Related Peptide; Calcium-Calmodulin-Dependent Protein Kinases; Carcinoma, Non-Small-Cell Lung; Class I Phosphatidylinositol 3-Kinases; Death-Associated Protein Kinases; DNA Methylation; Female; Homeodomain Proteins; Humans; Lung Neoplasms; Male; Middle Aged; Phosphatidylinositol 3-Kinases; Promoter Regions, Genetic; Protein Precursors; Tumor Suppressor Proteins

We identified an antigen recognized on a human non-small-cell lung carcinoma by a cytotoxic T lymphocyte clone derived from autologous tumor-infiltrating lymphocytes. The antigenic peptide is presented by HLA-A2 and is encoded by the CALCA gene, which codes for calcitonin and for the alpha-calcitonin gene-related peptide. The peptide is derived from the carboxy-terminal region of the preprocalcitonin signal peptide and is processed independently of proteasomes and the transporter associated with antigen processing. Processing occurs within the endoplasmic reticulum of all tumoral and normal cells tested, including dendritic cells, and it involves signal peptidase and the aspartic protease, signal peptide peptidase. The CALCA gene is overexpressed in medullary thyroid carcinomas and in several lung carcinomas compared with normal tissues, leading to recognition by the T cell clone. This new epitope is, therefore, a promising candidate for cancer immunotherapy.

Topics: Amino Acid Sequence; Antigens, Neoplasm; Base Sequence; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; DNA, Complementary; DNA, Neoplasm; HLA-A2 Antigen; Humans; Lung Neoplasms; Molecular Sequence Data; Proteasome Endopeptidase Complex; Protein Precursors; Protein Processing, Post-Translational; Protein Sorting Signals; RNA, Small Interfering; T-Lymphocytes, Cytotoxic; Transfection