calca-protein--human and Lung-Neoplasms

Accumulating evidence has demonstrated that gene alterations play a crucial role in LUAD development, progression, and prognosis. The present study aimed to identify the hub genes associated with LUAD. In the present study, we used TCGA database to screen the hub genes. Then, we validated the results by GEO datasets. Finally, we used cBioPortal, UALCAN, qRT-PCR, HPA database, TCGA database, and Kaplan-Meier plotter database to estimate the gene mutation, gene transcription, protein expression, clinical features of hub genes in patients with LUAD. A total of 5930 DEGs were screened out in TCGA database. Enrichment analysis revealed that DEGs were involved in the transcriptional misregulation in cancer, viral carcinogenesis, cAMP signaling pathway, calcium signaling pathway, and ECM-receptor interaction. The combining results of MCODE and CytoHubba showed that ADCY8, ADRB2, CALCA, GCG, GNGT1, and NPSR1 were hub genes. Then, we verified the above results by GSE118370, GSE136043, and GSE140797 datasets. Compared with normal lung tissues, the expression levels of ADCY8 and ADRB2 were lower in LUAD tissues, but the expression levels of CALCA, GCG, GNGT1, and NPSR1 were higher. In the prognosis analyses, the low expression of ADCY8 and ADRB2 and the high expression of CALCA, GCG, GNGT1, and NPSR1 were correlated with poor OS and poor PFS. The significant differences in the relationship of the expression of 6 hub genes and clinical features were observed. In conclusion, 6 hub genes will not only contribute to elucidating the pathogenesis of LUAD and may be potential therapeutic targets for LUAD.

Topics: Adenocarcinoma of Lung; Adenylyl Cyclases; Aged; Biomarkers, Tumor; Calcitonin Gene-Related Peptide; Databases, Genetic; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Glucagon; GTP-Binding Protein gamma Subunits; Humans; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prognosis; Protein Interaction Maps; Receptors, Adrenergic, beta-2; Receptors, G-Protein-Coupled; Transcriptome

Serum procalcitonin (PCT) is a biomarker used routinely to diagnose infections. Some malignancies are usual false positives for PCT. However, its value and behavior in the setting of lung cancers are poorly known. The objective of this study was to assess PCT positivity in a lung cancer cases series.. Between November 2011 and September 2012, all cases of newly diagnosed lung cancer with a pre-antineoplastic PCT assay and no patent signs of infection were included in the study. All PCT levels were assessed by immunofluorescent assay in a single laboratory.. Eighty-nine patients were included (70.8% male; mean age 62; small-cell cancer 20.2%; stage IV cancer 60.7%). Overall, PCT was positive in 42%. A neuroendocrine component, having 2 or more metastatic sites, having a pleura or a liver metastasis, and being positive for CRP were all significantly associated with positive PCT in univariate analysis. In multivariate analysis, only the presence of a neuroendocrine component remained strongly associated with a positive PCT (AOR=7.24 [CI=95% 1.91-27.51]; P=0.004). Finally, baseline PCT levels <0.5 µg/l were found in 43% of NSCLC with a neuroendocrine component, vs. 9% of cancers with other histology (P=0.0001).. Lung cancer may cause false positives for procalcitonin, particularly in cases of neuroendocrine cancers or in the presence of multiple metastases. These results should be taken into account for PCT-based decisional algorithms.

Topics: Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; False Positive Reactions; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Protein Precursors; Retrospective Studies; Time Factors

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

Procalcitonin (PCT) is widely used for the diagnosis of bacterial infections. The aim of this study was to evaluate PCT as a tumor and as a prognostic marker in patients with primary lung cancer.. We retrospectively performed a PCT dosage in the frozen serum samples of 147 patients with pulmonary neoplasia for whom a test of neuron-specific enolase (NSE) had been conducted at the time of diagnosis.. We show that a PCT serum level above 0.15 ng/mL was independently linked to the presence of a neuroendocrine component in the tumor (HR=5.809 95% CI [1.695-19.908] p: 0005). Thus, median PCT serum levels were significantly more elevated in small-cell lung cancers than in pulmonary adenocarcinomas: 0.33 ng/mL versus 0.07 ng/mL (p<0.001). However, the diagnostic value of serum PCT levels for diagnosing carcinoma with a neuroendocrine component remains low (sensitivity 63.8%; specificity 71.9%). In this series, serum PCT levels were significantly more elevated in the presence of liver metastases: 0.37 ng/mL versus 0.09 ng/mL in the absence of liver metastasis (p<0.001). In uni- and multivariate analyses, a serum PCT level above 0.15n g/mL and the presence of metastases and of sepsis at the time of diagnosis were independent factors of unfavorable prognosis.. Serum PCT is elevated in patients with lung cancer with neuroendocrine component or with liver metastases. As a consequence, in this population, PCT has a poor specificity for bacterial infection. At diagnosis, an elevated serum PCT is an independent predictive factor of bad prognosis.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Neuroendocrine Tumors; Prognosis; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Small Cell Lung Carcinoma

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

Postoperative infections and cardiac events are the major morbidity factors after thoracic surgery and dominating causes of death. Therefore, a sensitive blood marker is needed for an early diagnosis of complications. Twenty-two patients admitted with lung cancer were enrolled in this study. Procalcitonin, brain natriuretic peptide, C-reactive peptide and interleukin-6 levels were recorded preoperatively and postoperatively on days 1-5. Laboratory values of patients with cardiac or infectious complications were compared to patients without complications. During postoperative course procalcitonin and brain natriuretic peptide levels elevated in all patients, but both had higher peak levels in patients with infectious or cardiac complication than without these complications. Interleukin-6 levels were increased on day one and showed a slower decrease in case of complications than without complications. In general, brain natriuretic peptide and procalcitonin levels are increased in the postoperative course after major pulmonary resection, but cardiac and infectious complications are associated with higher levels and a slower decrease than without complications. Interleukin-6 levels showed a slower decrease in patients with complications in the postoperative course than without complications. So the combination of procalcitonin, brain natriuretic peptide, and interleukin-6 seems to be useful for an optimized postoperative monitoring.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Follow-Up Studies; Heart Diseases; Humans; Interleukin-6; Leukocyte Count; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Pneumonectomy; Predictive Value of Tests; Prospective Studies; Protein Precursors; Surgical Wound Infection; Time Factors; Treatment Outcome

The twofold aim of this prospective clinical study was to assess the accuracy of procalcitonin as a marker of postoperative infection after thoracic surgery and to compare it with C-reactive protein.. Procalcitonin and C-reactive protein concentrations, clinical symptoms of infection and systemic inflammation were recorded preoperatively and 5 days postoperatively in 157 patients undergoing the following procedures: 52 wedge resections, 28 pneumonectomies and 77 lobectomies (or bilobectomies). Patients were classified as non-infected or infected according to predefined criteria.. In non-infected patients (n=132), procalcitonin peaked on day 1 and C-reactive protein, on day 2. The procalcitonin value was significantly higher in patients having undergone a pneumonectomy (0.73+/-0.78 versus 0.54+/-0.25 ng/mL for lobectomy and 0.50+/-0.35 ng/mL for wedge resection; P=0.04). The mean value of procalcitonin was significantly higher in patients with postoperative infection (n=25) than in those with no postoperative infection (3.6+/-5.5 versus 0.63+/-0.62 ng/mL; P=0.0001). The onset of infection most frequently occurred on postoperative day 2 (43% of patients); maximum procalcitonin and C-reactive protein concentrations most frequently appeared on postoperative day 1 (56% of patients) and day 2 (63% of patients), respectively. The best cutoff value for detection of infection with procalcitonin was 1 ng/mL and with C-reactive protein, 100mg/L. Comparing the area under the Receiver Operating Characteristic curves, procalcitonin was better than C-reactive protein for detecting postoperative infection (0.92 versus 0.66; P<0.0001).. Procalcitonin can be used as a reliable diagnostic parameter to detect and to monitor infectious complications in the postoperative period after thoracic surgery, especially in patients felt to be at higher risk (SIRS). It provides more information about the course of the disease than C-reactive protein does, and can be detected before the occurrence of clinical infection.

Topics: Adult; Aged; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Postoperative Period; Protein Precursors; Sensitivity and Specificity; Surgical Wound Infection

Immunoreactive calcitonin (CT) secreted by DMS 53, a cell line derived from human small cell carcinoma of the lung, consists almost entirely of molecular species larger than the mature hormone (Mr 3,420). Messenger RNA isolated from DMS 53 cells and nude mouse tumors was translated in wheat germ systems, and the products were precipitated with CT-specific antisera. Analyses of the translation products by electrophoresis on 15% polyacrylamide-sodium dodecyl sulfate gels indicated synthesis of a Mr 16,500 preprohormone that was reduced to Mr 14,500 by cotranslation with microsomal membranes. Immunoprecipitation of CT from media from pulse-labeled cultures revealed two major products (Mr 16,500 and Mr 14,500) and up to three minor secreted polypeptides (Mr 9,400, 8,400, and 6,800). Intracellular CT from cell homogenates appeared almost entirely as a single major product (Mr 14,500) and possibly 3-4 minor components (Mr 16,500; 9,200, 8,400, and 6,800). No glycosylated forms of CT were demonstrable by lectin binding methods or labeling attempts with tritiated sugars. The presence of multiple CT species in DMS 53 cells suggests significant post-translational processing of the larger precursor molecules and the accumulation and secretion by small cell carcinoma of the lung of several intermediate immunoreactive forms via a glycosylation-independent secretory pathway.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Small Cell; Cell Line; Glycoproteins; Humans; Lung Neoplasms; Molecular Weight; Protein Precursors; Protein Processing, Post-Translational