big-gastrin and Lung-Neoplasms

The use of chromogranin A (CGA) as a circulating biomarker in lung carcinoids (LCs) is limited by low specificity and sensitivity. This study aimed to evaluate plasma progastrin-releasing peptide (ProGRPp) as an alternative to plasma CGA (CGAp), for the diagnosis and follow-up of LC.. ProGRPp and CGAp concentrations were measured in 107 patients with LC and 105 patients with benign lung disease (BLD).. ProGRPp distinguished patients with LC with active disease in the pretreatment (n = 43) and post-treatment (n = 43) groups from those with BLD: area under the curve for both 0.864 (p < 0.0001); sensitivity 67.4% and 58.1%, respectively; specificity 96.2%; at 64 pg/mL cutoff. CGAp failed to differentiate both LC groups from those with BLD: area under the curve 0.579 and 0.526 (for both p > 0.1); sensitivity 34.9% and 25.6%, respectively; specificity 73.3%; at 104 ng/mL cutoff. Only ProGRPp correlated with the Ki67 proliferation index (r = 0.40, p < 0.001) and was associated with mitotic count (p = 0.025), stage (p = 0.018), grade (p = 0.019), and the expression of thyroid transcription factor-1 (p = 0.005). ProGRPp had a high sensitivity (92.3%) in LC with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Abnormal postoperative ProGRPp level was associated with residual disease (p = 0.029). The changes in ProGRPp level during treatment, a decrease greater than 30% and an increase greater than 8%, were associated with image-based outcomes, partial response and disease progression, respectively (p < 0.0001). CGAp did not reflect the disease course.. ProGRPp was superior to CGAp in diagnosing LC with correlations concerning proliferation, grading, staging, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia co-occurrence, and response to treatment. ProGRPp is an optimal emerging biomarker to be further evaluated.

Topics: Biomarkers, Tumor; Carcinoma, Neuroendocrine; Chromogranin A; Disease Progression; Humans; Hyperplasia; Lung; Lung Neoplasms; Neuroendocrine Tumors; Peptides

Topics: Carcinoma, Neuroendocrine; Chromogranin A; Humans; Lung; Lung Neoplasms; Neuroendocrine Tumors; Peptides

Lung cancer is one of the most common cancer, there is a significant difference between the treatment and prognosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC tumor cells usually express neuroendocrine tumor (NET) markers, among which there are many studies on chromogranin A (CgA), synaptophysin (Syn), neuronspecific enolase (NSE) and pro-gastrin-releasing peptide (Pro-GRP) with SCLC. The levels of CgA, NSE and pro-GRP were related to the stage of SCLC, which were significantly higher in patients with extensive stage than in patients with limited stage, and their expression was significantly correlated with lower survival rate. Syn as an auxiliary diagnostic index of SCLC is more sensitive than CgA, and has high practical value in the differential diagnosis of SCLC and poorly differentiated squamous cell carcinoma; NSE is the most commonly used tumor marker in SCLC; Pro-GRP has stronger diagnostic advantages than CEA and NSE in distinguishing SCLC from NSCLC. Although these net markers are not specific markers of SCLC, their combined use with each others or combined with CT as an auxiliary diagnostic index may improve the level of differential diagnosis of SCLC, and they have a certain value in the staging of the disease, which is very important for the formulation of SCLC treatment strategy, their detection is conducive to the prevention and control of the disease.. 肺癌是常见的癌症之一，小细胞肺癌（SCLC）与非小细胞肺癌（NSCLC）在治疗和预后上有显著差异。SCLC的肿瘤细胞可表达一些神经内分泌肿瘤（NET）标志物，其中关于嗜铬粒蛋白A（CgA）与突触素（Syn）和神经元特异性烯醇化酶（NSE）及胃泌素释放肽前体（Pro-GRP）与SCLC的相关研究较多。CgA、NSE及Pro-GRP水平均与SCLC的分期有关，广泛期患者其水平显著高于局限期患者，且其表达与较低的生存率显著相关。Syn作为SCLC的辅助诊断指标时敏感度高于CgA，且在SCLC与低分化鳞癌的鉴别诊断中有较高的实用价值；NSE是目前临床上SCLC中使用最多的肿瘤标志物；Pro-GRP在SCLC与NSCLC的区分上具有强于CEA和NSE的诊断优势。尽管这些NET标志物均不是SCLC的特异性标志物，但它们联合运用或作为辅助诊断指标与CT联合使用或许能提高对SCLC的鉴别诊断水平，且它们在疾病的分期上有一定的价值，而疾病分期对SCLC治疗策略的制定十分重要，它们的检测有利于疾病的预防和控制。.

Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Chromogranin A; Gastrins; Humans; Lung Neoplasms; Peptide Fragments; Phosphopyruvate Hydratase; Protein Precursors; Small Cell Lung Carcinoma; Synaptophysin

The diagnostic value of six tumor markers was investigated and the appropriate combinations of those tumor markers to discriminate small cell lung cancer was explored.. Patients suspected with lung cancer (1938) were retrospectively analyzed. Candidate tumor markers from carcinoembryonic antigen (CEA), squamous cell carcinoma-related antigen (SCC), cytokeratin 19 fragment 21-1 (CYFRA 21-1), neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), and progastrin releasing peptide (ProGRP) were selected to construct a logistic regression model. The receiver operating characteristic curve was used for evaluating the diagnostic value of the tumor markers and the predictive model.. ProGRP had the highest positive rate (72.3%) in diagnosed small cell lung cancer, followed by neuron-specific enolase (68.3%), CYFRA21-1 (50.5%), carcinoembryonic antigen (45.5%), tissue polypeptide antigen (30.7%), and squamous cell carcinoma-related antigen (5.9%). The predictive model for small cell lung cancer discrimination was established, which yielded the highest area under the curve (0.888; 95% confidence interval: 0.846-0.929), with a sensitivity of 71.3%, a specificity of 95.0%, a positive predictive value of 49.0%, and a negative predictive value of 98.0%.. Combining tumor markers can improve the efficacy for small cell lung cancer discrimination. A predictive model has been established in small cell lung cancer differential diagnosis with preferable efficacy.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Gastrins; Humans; Keratin-19; Lung Neoplasms; Phosphopyruvate Hydratase; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Serpins; Small Cell Lung Carcinoma; Tissue Polypeptide Antigen

背景 在欧洲和中国进行Elecsys®胃泌素释放肽前体（ProGRP）免疫检测的多中心评估研究。方法 在欧洲的3个中心和中国的2个中心，在肺癌中，通过不精密度、稳定性、方法学比较和鉴别诊断能力来评价该检测法。结果 5个分析物浓度的中间不精密度范围为变异系数：2.2%-6.0%。在不同储存条件下，血浆和血清样本均显示出良好的稳定性。在血浆中Elecsys®和ARCHITECT检测（斜率1.02，截距-2.72 pg/mL）之间表现出良好的相关性。同时，Elecsys®检测在血清和血浆样本之间表现出良好的相关性（斜率0.93，截距2.35 pg/mL；相关系数0.97）。ProGRP作为不受种族、年龄、性别或吸烟史相关影响的检测手段，可鉴别小细胞和非小细胞肺癌（NSCLC）；截断值为84 pg/mL时，曲线下面积为0.90，95%CI: 0.87-0.93；敏感性为78.3%，特异性为95%。ProGRP浓度中位数在良性病变（38 pg/mL）、其他恶性肿瘤（40 pg/mL）或NSCLC（39 pg/mL）中较低，而在3期以上慢性肾脏疾病中浓度较高（>100 pg/mL）。结论 Elecsys® ProGRP检测在血清和血浆中稳定性增加，较现有检测法明显更具优势。ProGRP检测在中国的首次评价在不同种族中显示出相当的鉴别能力。.

Topics: Adult; Aged; China; Europe; Female; Gastrin-Releasing Peptide; Gastrins; Humans; Immunoassay; Lung Neoplasms; Male; Middle Aged; Protein Precursors

Peptide imprinted polymers were developed for detection of progastrin releasing peptide (ProGRP); a low abundant blood based biomarker for small cell lung cancer. The polymers targeted the proteotypic nona-peptide sequence NLLGLIEAK and were used for selective enrichment of the proteotypic peptide prior to LCMS based quantification. Peptide imprinted polymers with the best affinity characteristics were first identified from a 96-polymer combinatorial library. The effects of functional monomers, crosslinker, porogen, and template on adsorption capacity and selectivity for NLLGLIEAK were investigated and optimized. Ultimately, a solid phase extraction method was developed for highly selective enrichment of the target peptide from tryptic digests.

Topics: Adsorption; Amino Acid Sequence; Biomarkers, Tumor; Gastrins; Humans; Lung Neoplasms; Molecular Imprinting; Peptides; Protein Precursors; Small Cell Lung Carcinoma; Solid Phase Extraction

Progastrin-releasing peptide (proGRP) is a specific tumor marker in patients with small cell lung carcinoma (SCLC). It has been reported that serum proGRP levels rarely are elevated in patients with nonsmall cell lung carcinoma (NSCLC); the reported frequency is <3%. The purpose of this study was to examine the clinicopathologic features of NSCLC patients with high serum proGRP levels.. The authors measured serum proGRP levels with a TND-4 kit, a newly developed enzyme-linked immunoadsorbent assay, in 544 NSCLC and 206 SCLC patients. Pathologic features were examined using conventional hematoxylin and eosin staining and histochemical and immunohistochemical staining using polyclonal antibodies to proGRP, chromogranin A, calcitonin, and monoclonal antibody to the neural cell adhesion molecule (NCC-Lu-243).. The serum proGRP levels were elevated in 140 SCLC patients (68.0%) and in 23 NSCLC patients (4.2%). Seven of these 23 NSCLC patients had serum proGRP levels > or = 100 pg/mL. They included two patients with renal dysfunction, one patient diagnosed cytologically with adenocarcinoma without undergoing precise pathologic examination, two patients diagnosed histologically with squamous cell carcinoma with foci of small cell elements, and two patients diagnosed with large cell neuroendocrine carcinoma and poorly differentiated adenocarcinoma, respectively, which showed neuroendocrine differentiation on immunohistologic analysis. The remaining 16 NSCLC patients had serum proGRP levels < 70 pg/mL.. Nearly all NSCLC patients had serum proGRP levels < 100 pg/mL. However, if an NSCLC patient presents with a proGRP level > or = 100 pg/mL, the clinicopathologic features must be examined with regard to the small cell component, neuroendocrine differentiation, and renal dysfunction.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Humans; Lung Neoplasms; Male; Middle Aged; Protein Precursors; Renal Insufficiency

Using a library of radioimmunoassays against essential sequences of human progastrin and procholecystokinin, we have examined the occurrence of gastrin, cholecystokinin, and their precursors in bronchogenic adenocarcinomas, large-cell, small-cell, and squamous-cell carcinomas (n = 17). Progastrin and some of its bioactive (i.e., alpha-carboxyamidated) products were present in all tumors, irrespective of histological classification. The concentration of progastrin varied from 0.2 to 21.9 pmol/g tissue; glycine-extended intermediates constituted less than 0.1 to 0.5 pmol/g; and bioactive, carboxyamidated gastrin ranged from less than 0.1 to 6.1 pmol/g. Chromatography showed that the bioactive gastrins were exclusively gastrin-17 peptides, half of which were tyrosine O-sulfated. Neither procholecystokinin nor its processing products were found in the tumor extracts. Six samples of nonneoplastic human lung tissue contained traces of progastrin (range, less than 0.1-0.8 pmol/g), but neither bioactive gastrins nor any cholecystokinin. The results show that the gastrin gene is expressed in all classes of bronchogenic carcinomas. Due to incomplete posttranslational processing measurement of progastrin may be necessary to detect such expression.

Topics: Base Sequence; Carcinoma, Bronchogenic; Cholecystokinin; Chromatography, Gel; Gastrins; Humans; Lung Neoplasms; Neoplasm Proteins; Protein Precursors

Most peptide hormone assays measure only fully processed bioactive peptides. Such assays are unsuited to detect hormone gene expression by alternative or attenuated prohormone processing (tissue- or cell-specific processing). The gastrin system is expressed in several different tissues and is therefore useful for studies of tissue-specific processing. Consequently we have developed a simple processing-independent radioimmunoanalysis for progastrin. Using antisera against the NH2-terminus of a sequence, devoid of processing sites (preprogastrin76-86) after trypsination of neighboring cleavage sites, the assay quantitates the mRNA product irrespective of degree of processing. Used together with a conventional assay for the mature carboxyamidated gastrins, the processing-independent analysis shows that in different tissues only 1 to 55% of the total translation product is processed to bioactive gastrins. Thus processing-independent analysis greatly improves the detection of gastrin gene expression at the peptide level. The principle of the assay should be applicable to all protein and peptide systems.

Topics: Amino Acid Sequence; Chromatography, Gel; Gastric Mucosa; Gastrinoma; Gastrins; Humans; Lung Neoplasms; Molecular Sequence Data; Peptide Fragments; Protein Precursors; Protein Processing, Post-Translational; Radioimmunoassay; Trypsin