gastrin-releasing-peptide and Small-Cell-Lung-Carcinoma

The purpose of this study was to assess the diagnostic sensitivity and specificity for serum pro-gastrin-releasing peptide (Pro-GRP) in diagnosis of small cell lung cancer (SCLC) through pooling all the open published data.. Databases of PubMed, Cochrane, ISI Web of Knowledge, and CNKI were electronic, searched by two reviewers to find the diagnostic study serum Pro-GRP in diagnosis of SCLC. The diagnostic sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic (ROC) were calculated by Med DiSc1.4 software.. Finally, 21 studies were included in this meta-analysis. Because of statistical heterogeneity, the specificity, specificity, positive/negative likelihood ratio, and DOR were pooled by random effect model. The pooled sensitivity, specificity, PLR, NLR, DOR, and area under the ROC were 64% (95% confidence interval [CI]: 62%-66%), 94% (95% CI: 94%-95%), 11.87% (95% CI: 8.62-11.35), 0.32% (95% CI: 0.26%-0.39%), 40.98% (95% CI: 27.77%-60.64%), and 0.94 (95% CI: 0.91%-0.96%).. Serum Pro-GRP was promising biomarker for SCLC diagnosis.

Topics: Biomarkers, Tumor; Gastrin-Releasing Peptide; Humans; Odds Ratio; Publication Bias; ROC Curve; Sensitivity and Specificity; Small Cell Lung Carcinoma

To highlight the research progress of roles of bombesin-like peptides and their receptors in pharmacology and physiology.. Several new bombesin-derived radioactive or nonradioactive compounds were designed for the diagnosis and therapy of tumors that are overexpressing bombesin receptors. Both gastrin-releasing peptide receptor and neuromedin B receptor activation were shown to induce membrane depolarization and excite neurons in brain. Bombesin receptor subtype-3 was found to be downregulated in the muscle cells and myocytes from obese and type 2 diabetes patients, and its relevant cell signaling events in glucose homeostasis were also investigated. The molecular events triggered by bombesin receptors activation in different types of malignancies is being explored recently and new clues were provided for a better understanding of the biological roles of abnormal expression of bombesin receptors in tumors. Novel cross-talk between gastrin-releasing peptide receptor cell signaling and Sonic hedgehog pathways was identified in small-cell lung carcinoma.. Increasing evidence shows bombesin-like peptides and their receptors play important roles in both physiological state and diseases. More specific and safe tumor targeting Bombesin derivatives are being developed for tumor diagnosis and therapy.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Bombesin; Down-Regulation; Gastrin-Releasing Peptide; Humans; Intracellular Signaling Peptides and Proteins; Lung Neoplasms; Muscle, Skeletal; Peptide Fragments; Receptors, Bombesin; Small Cell Lung Carcinoma; Tumor Cells, Cultured

Lung cancer is the most common cancer, and small-cell lung cancer (SCLC) accounts for around 20 % of lung cancers. SCLC has a neuroendocrine cellular origin, and the tumor cells usually express neuroendocrine markers. There have been major recent advances in the management of SCLC, and multimodal approaches are now the norm. An improved knowledge of the prognostic variables would assist in defining which patients were better candidates to receive these newer intensive therapies. This single-center retrospective study of 97 previously untreated and histologically proven SCLC patients analysed the circulating neuroendocrine markers chromogranin A (CGA), pro-gastrin-releasing peptide (ProGRP), and neuron-specific enolase (NSE) in addition to the other more classical variables. Fifty patients had limited-stage disease and 47 had extensive disease. Sixty patients had an ECOG performance status (PS) of 0-1 and 37 had PS 2-4. Median survival for the whole study population was 13 months. Univariate analysis and univariate Cox regression modeling found a statistically significant association between survival and PS, disease stage, and CGA, ProGRP, and NSE levels. Age and sex were not prognostic. A shorter survival time was found in patients with a PS equal to or >2, extensive stage disease, a serum CGA level >56 ng/ml, a serum ProGRP level >58 pg/ml, and a serum NSE level >19 ng/ml. This study has found that there is a potential role for ProGRP, NSE, and CGA in both staging and prognosing survival in SCLC patients.

Topics: Adult; Aged; Biomarkers, Tumor; Chromogranin A; Female; Follow-Up Studies; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Phosphopyruvate Hydratase; Prognosis; Retrospective Studies; Small Cell Lung Carcinoma; Survival Rate

The serum levels of pro-gastrin-releasing peptide (proGRP), neuron-specific enolase (NSE), and chromogranin A (CgA) were studied in 69 patients with small cell lung cancer and 50 apparently healthy donors. A significant increase of all studied biochemical markers was revealed in small cell lung cancer patients, while the highest diagnostic efficiency was demonstrated by proGRP compared to NSE and CgA. ProGRP is a promising biochemical marker of small cell lung cancer, especially sensitive in patients with distant metastases (in the brain, liver, and bones).

Topics: Biomarkers, Tumor; Chromogranin A; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Phosphopyruvate Hydratase; Small Cell Lung Carcinoma

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan-Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.

Topics: Brain Neoplasms; Cranial Irradiation; Gastrin-Releasing Peptide; Humans; Incidence; Lung Neoplasms; Small Cell Lung Carcinoma

Topics: Algorithms; Biomarkers, Tumor; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Peptide Fragments; Phosphopyruvate Hydratase; Recombinant Proteins; Small Cell Lung Carcinoma

Testing for circulating biomarkers in lung cancer is hampered by the insufficient specificity. We aimed to assess the relative diagnostic accuracy of pro-gastrin-releasing peptide (ProGRP) for the differential diagnosis of small cell lung cancer and compare it with more conventional biomarkers.. We enrolled a cohort of 390 patients with a clinical suspicion of lung cancer and for whom a histologic assessment was available. Serum or plasma samples were assessed for ProGRP, carcinoembryonic antigen, CYFRA 21-2, and neuron-specific enolase. The performance of each biomarker in discriminating the small cell lung cancer and squamous cell carcinoma/adenocarcinoma from non-malignant lung disease, and small cell lung cancer from squamous cell carcinoma/adenocarcinoma, was assayed by receiver operating characteristic curve analysis.. At the cut-off levels suggested by the manufacturers, ProGRP and neuron-specific enolase showed an almost identical sensitivity of 55.2% and 55.6%, respectively, in discriminating small cell lung cancer with respect to non-malignant lung disease. In order to quantify the added value of ProGRP to other conventional markers, we ran a multivariable logistic regression analysis, but the results showed that no markers improve the performance of ProGRP.. ProGRP and neuron-specific enolase individually appear more accurate than other conventional biomarkers for small cell lung cancer, but the union of two markers does not increase the accuracy. The very small target group of patients with small cell lung cancer is a limitation of this study, which can explain why ProGRP alone does not show a sensitivity higher than neuron-specific enolase, as reported by other authors.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Follow-Up Studies; Gastrin-Releasing Peptide; Humans; Keratin-19; Lung Neoplasms; Male; Peptide Fragments; Prognosis; Recombinant Proteins; ROC Curve; Small Cell Lung Carcinoma

Pro-gastrin-releasing peptide (ProGRP) is the promising molecular tumor marker of small cell lung cancer (SCLC). Here we study the influence of different blood samples treatment methods on ProGRP.Serum with and without separation gel and heparin plasma from 10 SCLC patients and 5 healthy individuals were assayed for ProGRP immediately and 2, 4, 6, 8, 24, and 48 hours after collection.ProGRP of serum with and without separation gel and heparin plasma detected immediately was basically consistent, whereas there was a significant difference in the level of them assayed after 2 hours. No significant variation with time was observed in heparin plasma, but in serum with and without separation gel, ProGRP concentrations gradually declined with time, with statistical significance. When assayed within 2 hours, each time point of ProGRP in heparin plasma had no significant difference and the difference of PrpGRP in serum separating gel existed at 1.5 hours.Heparin plasma is the best option for clinical test of ProGRP. If serum with separation gel is used, optimization methods of turn-around-time which guarantee samples detected within 1 hour after collection can make results more instructive for clinical treatment.

Topics: Biomarkers, Tumor; Blood Specimen Collection; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Small Cell Lung Carcinoma; Time Factors

Pro-gastrin releasing peptide (ProGRP) plays the role of oncogene in small cell lung cancer (SCLC). In this study, we aim to explore the biological function of ProGRP in SCLC cells and its potential mechanism. Expression of ProGRP in SCLC tissues and cell lines were detected by immunohistochemistry and western blot analysis, respectively. The transduced cell lines with ProGRP down-regulation were established using RNA interference technology. Cell viability, cologenic, apoptosis-associated assay and the biomarker levels determination for cell supernatant were performed in the transduced cells to elucidate the biological functions and mechanisms of ProGRP in SCLC cells. Our data showed that ProGRP protein was demonstrated a higher level in SCLC tissues and cells compared with the control, and its diagnostic efficiency was better than NSE, further, the higher levels of ProGRP were detected in the patients with extensive disease stage (P < 0.05), were also the unfavorable factor to the prognosis of SCLC patients. Additionally, the concentration of serum ProGRP is a useful biomarker in disease-monitoring of the patients with SCLC. Down-regulation of ProGRP significantly reduced SCLC cell growth, repressed colony formation, but increased cancer cell apoptosis. Additionally, repression of ProGRP also induced change in the cell cycle and output of NSE. Our data indicated that ProGRP serve as the useful biomarker in the management of SCLC and might be a potential therapeutic target.

Topics: A549 Cells; Aged; Apoptosis; Biomarkers, Tumor; Case-Control Studies; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Down-Regulation; Female; Flow Cytometry; Gastrin-Releasing Peptide; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Sensitivity and Specificity; Small Cell Lung Carcinoma

Aptamers are single-strand oligonucleotides that are generated by the systemic evolution of ligands by exponential enrichment (SELEX) technique and that can bind to target molecules specifically. However, only a few aptamers have been developed to date against tumor markers. To utilize aptamers for tumor diagnosis, a variety of aptamers are required. Here, a single-stranded DNA aptamer specific for pro-gastrin-releasing peptide (proGRP), a marker for small cell lung cancer, was selected using SELEX. After selection, identical sequences were found in the DNA library. This sequence was selected and its binding affinity to proGRP was evaluated using surface plasmon resonance.

Topics: Aptamers, Nucleotide; Biomarkers, Tumor; DNA, Single-Stranded; Gastrin-Releasing Peptide; Humans; Kinetics; Lung Neoplasms; SELEX Aptamer Technique; Small Cell Lung Carcinoma; Surface Plasmon Resonance

To evaluate the value of plasma ProGRP, CYFRA 21-1 and CEA in patients with lung cancer.. The levels of plasma ProGRP, CYFRA 21-1 and CEA were detected in 85 healthy control, 49 benign lung diseases and 143 lung neoplasms. The levels of ProGRP in the patients with SCLC was monitored.. The level of plasma ProGRP in SCLC (M 179.1 ng/ml) was significantly higher than adenocarcinoma (M 35.3 ng/ml), squamous-cell carcinoma (M 33.3 ng/ml), healthy control (M 35.6 ng/m) and benign lung diseases (M 33.3 ng/m), P < 0.001. The sensitivity and specificity for diagnosing SCLC by ProGRP were 60.6% and 95.0% respectively. In the effective treatment group, ProGRP reduced 45.9%, in the progression group, ProGRP increased 103.1%, P < 0.05. The level of CEA in the metastatic adenocarcinoma (M 10.22 ng/ml) was significantly higher than non-metastatic adenocarcinoma (M 3.85 ng/ml) and squamous cell carcinoma (M 2.56 ng/ml) (P < 0.01).. The plasma ProGRP is a good indicator for diagnosing and evaluating cure effect in SCLC; the high expression of CEA is related to the metastatic adenocarcinoma.

Topics: Adult; Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Case-Control Studies; Diagnostic Techniques and Procedures; Female; Gastrin-Releasing Peptide; Humans; Keratin-19; Lung Neoplasms; Male; Middle Aged; Small Cell Lung Carcinoma

Recent data suggest a link between chronic inflammation, angiogenesis, and the development of cancer. The aim of this study was the evaluation of serum IL-6 and VEGF in comparison with the tumor markers NSE and ProGRP, with respect to the prognosis of small cell lung cancer patients. The study of IL-6, VEGF, NSE, ProGRP and platelet count was performed in a group of 72 patients with previously untreated small cell lung cancer at different stages of disease: 40 with limited and 32 with extensive disease. Significantly higher IL-6 and VEGF concentrations and platelet count, as well as NSE and ProGRP levels, were found in patients with small cell lung cancer in comparison with the reference group. Patients with extensive cancer had significantly higher levels of IL-6, VEGF, NSE and ProGRP than those with limited cancer. Elevated VEGF levels, with no significant differences in frequency of elevated NSE and ProGRP concentrations, were often observed in patients with IL-6 levels higher than 5.1 ng/l. Univariate analysis confirmed a significant relationship not only between overall survival and stage of disease or gender, but also with VEGF, IL-6, NSE and ProGRP levels. Moreover, multivariate analysis revealed that only the extent of the disease and IL-6 may be independent prognostic factors in the group of small cell lung cancer patients under investigation. However, simultaneous determinations of ProGRP and IL-6, as well as ProGRP and VEGF, in addition to the extent of the disease, may serve as additional, independent prognostic factors in small cell lung cancer.

Topics: Aged; Female; Gastrin-Releasing Peptide; Humans; Interleukin-6; Lung Neoplasms; Male; Middle Aged; Models, Biological; Phosphopyruvate Hydratase; Platelet Count; Prognosis; ROC Curve; Small Cell Lung Carcinoma; Vascular Endothelial Growth Factor A