Serum Progastrin-releasing Peptide Research Articles

Identification of risk factors of EGFR-TKIs primary resistance in lung adenocarcinoma patients and construction of a risk predictive model: a case-control study.

Lung cancer is one of the malignancies with the highest incidence and mortality rates. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line treatment for patients with EGFR-mutated lung adenocarcinoma (LUAD). However, some patients with EGFR-sensitive mutations develop primary resistance to EGFR-TKIs. This study aims to analyze the clinical characteristics of LUAD patients with primary resistance to EGFR-TKIs, identify independent risk factors for primary resistance, and establish a risk predictive model to provide reference for clinical decision-making. We collected data from LUAD patients with EGFR-sensitive mutations (19del/21L858R) who were hospitalized in our institution between 2020 and 2022 and received first-generation EGFR-TKIs with follow-up exceeding 6 months. These patients were categorized into primary resistance and sensitive groups based on treatment outcomes. We compared general clinical data, laboratory tests, and tumor-related characteristics between the two groups, analyzed risk factors for primary resistance to EGFR-TKIs, and constructed a risk predictive model. The model's predictive value was comprehensively assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Serum neuron-specific enolase (NSE) concentration (P=0.03), serum pro-gastrin-releasing peptide (ProGRP) concentration (P=0.01), and Ki67 expression (P<0.001) were identified as independent risk factors for primary resistance to EGFR-TKIs in LUAD. The combined presence of these three risk factors had the highest predictive value [area under the curve (AUC) =0.975, P<0.001]. We constructed a predictive model for the risk of primary resistance to EGFR-TKIs in LUAD patients, incorporating these three parameters, and represented it through a visually interpretable nomogram. The calibration curve of the nomogram demonstrated its strong predictive ability. Further decision curve analysis indicated the model's clinical utility. Based on a single-center retrospective case-control study, we identified serum NSE concentration, ProGRP concentration, and Ki67 expression as independent risk factors for primary resistance to EGFR-TKIs in LUAD patients. We constructed and validated a risk predictive model based on these findings. This predictive model holds promise for clinical application, aiding in the development of personalized treatment strategies and providing a scientific basis for early identification of primary resistance patients.

Extracellular Vesicles Derived circSH3PXD2A Inhibits Chemoresistance of Small Cell Lung Cancer by miR-375-3p/YAP1.

Small cell lung cancer (SCLC) is a subtype of lung cancer with high malignancy and poor prognosis. Rapid acquisition of chemoresistance is one of the main reasons leading to clinical treatment failure of SCLC. Studies have indicated that circRNAs participate in multiple processes of tumor progression, including chemoresistance. However, the molecular mechanisms of circRNAs driving the chemoresistance of SCLC are not well specified. The differentially expressed circRNAs were screened by transcriptome sequencing of chemoresistant and chemosensitive SCLC cells. The EVs of SCLC cells were isolated and identified by ultracentrifugation, Western blotting, transmission electron microscopy, nanoparticle tracking analysis and EVs uptake assays. The expression levels of circSH3PXD2A in serum and EVs of SCLC patients and healthy individuals were detected by qRT‒PCR. The characteristics of circSH3PXD2A were detected by Sanger sequencing, RNase R assay, nuclear-cytoplasmic fraction assay, and fluorescence in situ hybridization assay. The mechanisms of circSH3PXD2A inhibiting SCLC progression were studied by bioinformatics analysis, chemoresistance assay, proliferation assay, apoptosis assay, transwell assay, pull-down assay, luciferase reporting assay, and mouse xenograft assay. It was identified that the circSH3PXD2A was a prominently downregulated circRNA in chemoresistant SCLC cells. The expression level of circSH3PXD2A in EVs of SCLC patients was negatively associated with chemoresistance, and the combination of EVs-derived circSH3PXD2A and serum ProGRP (Progastrin-releasing peptide) levels had better indications for DDP-resistant SCLC patients. CircSH3PXD2A inhibited the chemoresistance, proliferation, migration, and invasion of SCLC cells through miR-375-3p/YAP1 axis in vivo and in vitro. SCLC cells cocultured with EVs secreted by circSH3PXD2A-overexpressing cells exhibited decreased chemoresistance and cell proliferation. Our results manifest that EVs-derived circSH3PXD2A inhibits the chemoresistance of SCLC through miR-375-3p/YAP1 axis. Moreover, EVs-derived circSH3PXD2A may serve as a predictive biomarker for DDP-resistant SCLC patients.

Evaluating the diagnostic and prognostic value of serum TuM2-PK, NSE, and ProGRP in small cell lung cancer.

The aim of this study was to explore the diagnostic and prognostic value of serum tumor M2-pyruvate kinase (TuM2-PK), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) levels in patients with small cell lung cancer (SCLC). The levels of serum TuM2-PK, NSE, and ProGRP in 102 patients with SCLC, 60 patients with benign lung disease (BLD), and 90 healthy controls were detected. The serum TuM2-PK, NSE, and ProGRP levels in the SCLC group were higher than those in BLD group (p < 0.05) and healthy control group (p < 0.05). The sensitivity of TuM2-PK, NSE, and ProGRP detection in SCLC was 82.35%, 60.78%, and 77.45% respectively, and specificity was 91.11%, 81.11%, and 86.67%, respectively. The area under the curve (AUC) of SCLC resulting from TuM2-PK was significantly better than that of NSE and ProGRP. The application of TuM2-PK combined with NSE and ProGRP improved the diagnostic yield of SCLC patients and had better diagnostic value than TuM2-PK alone. Univariate and multivariate analysis indicated that an elevated TuM2-PK level was an independent prognostic factor for shorter survival in SCLC. These results suggest that TuM2-PK levels in the serum could be an effective biomarker for the diagnosis and prognosis of SCLC.

Association of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP with Clinicopathological Characteristics and Chemotherapeutic Outcomes of Lung Cancer.

The aim of this study was to investigate the association of serum carcinoembryonic antigen (CEA), nerve-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag), and pro-gastrin-releasing peptide (ProGRP) with the clinicopathological characteristics and chemotherapeutic outcomes of patients with lung cancer. A total of 189 patients with lung cancer (lung cancer group) diagnosed at the Fourth Affiliated Hospital of Anhui Medical University from January 2020 to December 2021 were included. During the same period, 199 patients with benign lung disorders were included as the benign lung disease group and 75 healthy people were selected as the control group. The serum concentrations of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP in all the 3 groups were analyzed and compared in patients with different lung cancer tumor-node-metastasis (TNM) stages and pathological classifications. Atotal of 11 patients with small cell lung cancer (SCLC) and 18 patients with lung adenocarcinoma (LAC) were further evaluated forthe dynamic changes of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP before chemotherapy and during the 6 courses of chemotherapy, and the outcome of chemotherapy was evaluated every 2 courses. The serum concentrations of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP in the lung cancer group were significantly higher than those in the control group (P < .05). We found statistically significant differences in serum CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP among patients with different pathological types (LAC, squamous cell carcinoma, or SCLC) and different stages (I-IV). The ProGRP and NSE had the highest expression in SCLC, CEA showed the highest expression in LAC, whereas CYFRA21-1 and SCC-Ag showed the highest expression in lung squamous cell carcinoma (LSCC). The concentrations of all the markers were elevated in the advanced pathological stages. The receiver operating characteristic curve analysis showed that the diagnostic value of the combined detection of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP for lung cancer was significantly higher than using a single biomarker (P < .05). Our dynamic monitoring results show that ProGRP progressively decreased in remission cases of SCLC and CEA progressively decreased in LAC remission cases. CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP have good clinical value in the early diagnosis, differential diagnosis, and progression monitoring of lung cancer. The ProGRP and CEA concentrations are beneficial for evaluating the outcome of chemotherapy in SCLC and LAC. The combined detection of multiple biomarkers shows improved clinical value in the early diagnosis of lung cancer.

Diagnostic value of serum tumor markers CEA, CYFRA21-1, SCCAg, NSE and ProGRP for lung cancers of different pathological types

To evaluate the diagnostic value of the serum tumor markers carcinoembryonic antigen (CEA), cytokeratin-19-fragment (CYFRA21-1), squamous cell carcinoma associated antigen (SCCAg), neuron-specificenolase (NSE) and pro-gastrin-releasing peptide (ProGRP) for lung cancers of different pathological types. This study was conducted among patients with established diagnoses of lung adenocarcinoma (LADC, n=137), lung squamous cell carcinoma (LSCC, n=82), small cell lung carcinoma (SCLC, n=59), and benign chest disease (BCD, n=102). The serum tumor markers were detected for all the patients for comparison of the positivity rates and their serum levels. ROC curve was used for analysis of the diagnostic efficacy of these tumor markers either alone or in different combinations. In patients with LADC, the positivity rate and serum level of CEA were significantly higher than those in the other groups (P < 0.05); the patients with LSCC had the highest positivity rate and serum level of SCCAg among the 4 groups (P < 0.05). The positivity rates and serum levels of ProGRP and NSE were significantly higher in SCLC group than in the other groups (P < 0.05). CYFRA21-1 showed the highest positivity rate and serum level in LADC group and LSCC group. With the patients with BCD as control, CEA showed a diagnostic sensitivity of 62.8% and a specificity of 93.1% for LADC, and the sensitivity and specificity of SCCAg for diagnosing LSCC were 64.6% and 91.2%, respectively. CYFRA21-1 had the highest diagnostic sensitivity for LADC and LSCC. The diagnostic sensitivity and specificity of ProGRP for SCLC were 83.1% and 98.0%, respectively. When combined, CYFRA21-1 and CEA showed a high sensitivity (78.8%) and specificity (86.3%) for diagnosing LADC with an AUC of 0.891; CYFRA21-1 and SCCAg had a high sensitivity (84.1%) and specificity (87.3%) for diagnosing LSCC with an AUC of 0.912. NSE combined with ProGRP was highly sensitive (88.1%) and specific (98.0%) for diagnosis of SCLC, with an AUC of 0.952. For lung cancers of different pathological types, the combination of all the 5 tumor markers showed no significant differences in the diagnostic power from a combined detection with any two of the markers (P>0.05). CEA, CYFRA21-1, SCCAg, NSE and ProGRP are all related to the pathological type of lung cancers and can be used in different combinations as useful diagnostic indicators for lung cancers.

New insights into the diagnostic characteristics and clinical application of serum biomarkers for lung cancer, and human epididymis protein 4 as a new biomarker?

The value of serum tumor biomarkers used for lung cancer diagnosis is still controversial in clinical practice. This study aimed to further dissect and evaluate the clinical value of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1) together with a potential new biomarker, the human epididymis protein 4 (HE4) for lung cancer diagnosis, in a large cohort of a Chinese population. Ostensibly healthy individuals, as well as those with benign non-cancerous diseases, benign tumors, lung cancers, and other types of malignancies, were enrolled in the study. Serum ProGRP, NSE, SCC-Ag, CEA, CYFRA21-1, and HE4 were analyzed using the chemiluminescence immunoassay. Data were analyzed utilizing the SPSS and GraphPad Prism software. Detailed dissection of the diagnostic characteristics of serum 6 biomarkers on lung cancer was performed. All 6 biomarkers showed capabilities in characterizing lung cancer from other diseases. ProGRP and NSE were highly specific to small cell lung cancer (SCLC); SCC-Ag was a fair biomarker for NSCLC, specifically SCC histotype; CEA showed specificity to SCLC, followed by NSCLC; CYFRA21-1 was a good biomarker for both SCLC and NSCLC; HE4 showed high specificity to SCLC. For NSCLC characterization, CYFRA21-1+HE4+CEA was the best combinatory pattern in the terms of diagnostic performance (AUC=0.8110). The best combinatory analysis for SCLC was ProGRP+NSE+HE4 (AUC=0.9282). Patients with advanced stage, larger tumor, males, and age 50 or older had higher serum biomarkers levels than those with early stage, smaller tumor, females, and age under 50. Six biomarkers had capabilities in characterizing lung cancer with high or fair diagnostic performance. HE4 is a potential biomarker for both SCLC and NSCLC diagnosis, which merits further investigation.

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti-GABABR encephalitis.

To improve the clinical understanding of anti-gamma-aminobutyric-acid B receptor encephalitis (anti-GABABR encephalitis) by analyzing 13 cases. We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti-GABABR encephalitis. Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro-gastrinreleasingpeptide (ProGRP) levels were found in 70% of patients with a median value of 490.10pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow-up (p>.05). The value between SCLC and non-SCLC subgroup was significantly different (p<.05). Ten patients received immunotherapy (three patients refused treatment). After immunotherapy, the frequency of seizures was significantly reduced. There was a significant difference in mRS between admission and after treatment (p<.05). The average survival time after onset was 27.7months. Epilepsy is the most common clinical manifestation of Anti-GABABR encephalitis. The prognosis of anti-GABABR encephalitis is poor. Section of anti-GABABR encephalitis patients have higher level of serum ProGRP and positive GSF oligoclonal bands. Elevated ProGRP or positive CSF oligoclonal bands with classic clinical features can potentially help to improve early recognition of anti-GABABR encephalitis.

Transformation from non-small cell lung cancer to small cell lung cancer: A report of clinicopathological characteristics and prognoses.

e15084 Background: The transformation to small cell lung cancer (SCLC) is one of the mechanisms of drug resistance in non-small cell lung cancer (NSCLC). However, there are few reports on it. The study aims to analyze the clinicopathological characteristics of the patients, to explore the transformation factors and reasonable treatment strategy for them. Methods: A total of 9 patients with pathologically diagnosed NSCLC transformed into SCLC after first-line or multi-line treatment were involved in the study. Results: Among the 9 patients, there were 8 adenocarcinomas (ADC) and 1 squamous cell carcinoma (SCC), 7 of them were non-smokers. Epidermal growth factor receptor (EGFR) mutations were present in all ADC patients, including 7 with exon19 deletion (87.5%) and 1 with exon21 mutation (12.5%). All of them received EGFR tyrosine kinase inhibitors (TKIs) before the transformation, and the median transformation time was 19.5 months (95% CI, 14.1-32.7months). After first-line chemotherapy with paclitaxel and cisplatin, one SCC patient transformed to SCLC within 5 months. EGFR mutation was still maintained in 6 ADC patients when transformation occurred, of which 2 patients had a new TP53 mutation and 1 had RB1 gene mutation. Serum tumor markers were monitored in 6 patients, of them, progastrin releasing peptide (Pro-GRP) increased apparently at the time of disease progression in 5 patients, and neuron-specific enolase (NSE) also increased in 3 patients. This phenomenon occurred three to six months earlier than the transformation. The median survival time (MST) was 37 months from the initial diagnosis of NSCLC and 13 months after transformation. The median progression-free survival (mPFS) was only 2 months for those treated with chemotherapy (CT) after transformation, whereas 6 months treated with CT combined with TKIs as the first-line treatment. Three patients who received chemotherapy combined with programmed death receptor-1 (PD-1) inhibitor after multi-line therapy underwent progress within 2 months, nevertheless, 1 patient treated with the EP regimen combined with pembrolizumab as the first line treatment after transformation had a PFS of 12 months. After re-progression, the patients got another PFS of 5 months with a pemetrexed-platinum combined with atezolizumab. Conclusions: Phenotypic transformation is one of the mechanisms of drug resistance for NSCLC patients, especially for those with EFGR exon19 deletion received EGFR-TKIs. Tumor heterogeneity, TP53 gene and Rb gene mutation may be responsible for the transformation. The serum Pro-GRP over expression could as an early predictor of transformation. Classical chemotherapy is ineffective after SCLC transformation patients who still have sensitive mutation, it might be suitable to combine with EGFR-TKIs. The early application of immunotherapy could be attempted, but still needs to be explored further.

Circulating pro-gastrin releasing peptide (ProGRP) in patients with medullary thyroid carcinoma.

Serum calcitonin (CT) is pivotal in medullary thyroid cancer (MTC) management. Recently, progastrin releasing peptide (ProGRP) has been proposed as a candidate complementary tumor marker of MTC. As current data are sparse our study was undertaken to evaluate the distribution of ProGRP in patients with MTC and its relationship with the tumor burden. Additionally, serial measurement of CT, carcinoembryonic antigen (CEA) and ProGRP was evaluated in three patients undergoing tyrosine kinase inhibitors (TKI). Seventy-eight, 125 and 62 sera from patients with MTC, non-medullary malignant and benign thyroid diseases were collected, respectively. ProGRP measurement was performed by Elecsys® assays on Cobas e601 platform (Roche Diagnostics). Significantly higher ProGRP levels were found in MTC compared to non-MTC patients. Among MTC patients ProGRP levels accurately discriminate patients with active from those with cured disease and, respectively, patients with loco-regional active disease from those with distant metastasis. Finally, ProGRP performed better than CT and CEA in monitoring the response to TKI therapy in three patients monitored serially. Serum ProGRP is promising as a complementary tumor marker in MTC patients. Further studies will be required, mainly focused on monitoring ProGRP during TKI treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and carcinoembryonic antigen.

Detecting Lung Cancer Stages Earlier By Appropriate Markers Rather Than Biopsy And Other Techniques

Abstract Introduction/Objective Early detection of lung cancer stages is deeply under consideration of scientists. By day, high rate of mortality might be caused by cancer of lung over the world. The biopsy is still the golden standard as a histological predictor to determine lung cancer worldwide. However, a biopsy has various complications and hardness especially in collecting tissue samples. Therefore, detecting appropriate tools to determine the early stages of lung cancer is urgently needed. Some biomarkers levels have been determined in patient’s serum. The correlation between studied biomarkers and lung cancer has been studied by current research to avoid biopsy and other techniques. Methods The various biomarkers such as (CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4) were measured and calculated in 379 infected cases with lung cancer. Also, the same parameters were determined in 113 healthy persons as controls. Alternative markers’ levels were determined by using ELISA technique. Noninvasive markers were approved by comparison with CT chest scan and Biopsy techniques. Results Our research has indicated that Some of the studied biomarkers such as cytoskeleton-associated protein 4 (CKAP4), pro-gastrin-releasing peptide (ProGRP) and Prolactin (PRL) have high sensitivity from 77.05% to 96.72% and accuracy from 89.71% to 97.79% as well as their cut off which approved the aim of this study. However, other indicators (CEA, SCCA and CYFRA21-1) have low sensitivity from 62.49 % to 87.31% and accuracy between 71.27 % and 88.43 %. Meanwhile, CT scan has high sensitivity around 83% with specificity about 71%. Conclusion Alternative biomarkers (CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4) are considered as prospective markers to differentiate healthy individuals from lung cancer disease by their significant results in early stages detection. Thence, if serum CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4 are measured together, it would be the precise criterion of early levels of lung cancer rather than the lung biopsy definitely. However, further researches are needed to prove more reliable noninvasive markers of lung cancer.

Decline in serum progastrin-releasing peptide predicts the response of patients with small cell lung cancer to chemotherapy.

The utility of serum progastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) as biomarkers for treatment monitoring and as prognostic factors was investigated in small cell lung cancer (SCLC) patients. Patients were first diagnosed pathologically at the First Affiliated Hospital of the University of Science and Technology of China and had their serum ProGRP and NSE levels measured using an electrochemiluminescence immunoassay. A total of 120 SCLC patients were enrolled. In responsive patients, ProGRP levels decreased significantly following two cycles of chemotherapy and continued to decline over the course of treatment. However, this decrease in ProGRP levels was not observed in non-responsive patients. Changes in ProGRP levels were more accurate than changes in NSE levels for monitoring the effects of chemotherapy in patients with SCLC. Following two treatment cycles or after the occurrence of drug resistance, changes in ProGRP levels in patients with low ProGRP levels at the time of diagnosis were not notably, regardless of whether or not patients were responders. The area under the receiver operating characteristic curve of the decline in ProGRP levels as a therapeutic biomarker of SCLC was 0.9643, and the cut-off value was 55.02%. A decline in ProGRP levels maybe a good predictor of objective response to chemotherapy in patients with SCLC with higher ProGRP levels at diagnosis. This model is expected to replace or be combined with imaging to predict chemotherapeutic treatment effects in patients with SCLC.

Serum ProGRP as a novel biomarker of bone metastasis in prostate cancer

BackgroundThe prognosis of prostate cancer (PCa) is related to tumor metastasis, among which 80% were bone metastasis. In this study, we investigated the correlation between diverse clinical factors and bone metastasis in PCa patients and identified potential biomarkers of bone metastasis in PCa patients. MethodsThe clinical data of 150 PCa patients were reviewed consecutively from January 2015 to March 2020 in this study. The relationships between clinical characteristics, serum biomarkers and bone metastasis in PCa patients were analyzed, respectively. Multivariate logistic regression analysis was applied to identify potential markers of bone metastasis in prostate cancer. Receiver operating characteristic (ROC) curve was used to explore the diagnostic values of potential biomarkers. ResultsCompared with the PCa patients without bone metastasis, the serum levels of CA-125, T-PSA, F-PSA, CYFRA21-1 and ProGRP were significantly elevated in PCa patients with bone metastasis. Multivariate logistic regression analysis showed that T-PSA (OR 1.014, P = 0.021), F-PSA (OR 1.124, P = 0.016) and Pro-gastrin-releasing peptide (ProGRP) (OR 1.057, P = 0.026) were significantly associated with the bone metastasis of PCa patients. ROC curves indicated that T-PSA, F-PSA and ProGRP could effectively discriminate bone metastasis from non-bone metastasis PCa patients, and the AUCs (area under the curves) were 0.885, 0.919 and 0.752, respectively. According to the Youden index, the cut-off values of T-PSA, F-PSA and ProGRP were defined as 56.50 ng/ml, 6.96 ng/ml and 31.60 pg/ml, respectively. T-PSA, F-PSA and ProGRP produced a sensitivity of 78.30%, 81.70% and 61.70%, a specificity of 93.30%, 88.90% and 82.20%, respectively. The AUC for the combination of T-PSA, F-PSA with ProGRP was 0.941 with 90.00% sensitivity, much better than that of any single biomarker or two biomarkers combinate. ConclusionsSerum ProGRP might be a potential tumor marker of bone metastasis in prostate cancer, which may contribute to the early diagnosis of bone metastasis when used alone or in combination with other commonly used biomarkers.

ProGRP as a Novel Biomarker for the Differential Diagnosis of Medullary Thyroid Carcinoma in Patients with Thyroid Nodules

Objective: To investigate the release of progastrin-releasing peptide (ProGRP) in patients with thyroid nodules and the value of ProGRP in fine-needle aspirate washout fluid (FNA-ProGRP) in the differential diagnosis between medullary thyroid carcinoma (MTC) and non-MTC thyroid nodules. Methods: We investigated 2,446 healthy persons and 212 patients with 235 thyroid nodules. They were classified into healthy, nodular goiter, chronic thyroiditis, thyroid follicular neoplasm, papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. The serum ProGRP and FNA-ProGRP were measured. Results: The serum ProGRP median concentration in MTC was 124.40 pg/mL, significantly higher than in other groups. The cutoff value of serum ProGRP was 68.30 pg/mL, leading to 53.85% sensitivity, 96.98% specificity, and 0.51 kappa value in MTC. The FNA-ProGRP median concentration in MTC nodules was 2,096.00 pg/mL, significantly higher than in other groups. A receiver operating characteristic analysis of MTC nodules and non-MTC nodules indicated that the cutoff value was 22.77 pg/mL, leading to 94.12% sensitivity, 98.27% specificity, and 0.85 kappa value. Conclusion: FNA-ProGRP measurement could be served as an ancillary method for the differential diagnosis between MTC and non-MTC thyroid nodules. Abbreviations: CEA = carcinoembryonic antigen; CT = calcitonin; FNAC = fine-needle aspiration cytology; FNA-CT = calcitonin in fine-needle aspirate washout fluid; FNA-ProGRP = ProGRP in fine-needle aspirate washout fluid; MTC = medullary thyroid carcinoma; ProGRP = progastrin-releasing peptide; SCLC = small-cell lung cancer; TM = tumor marker.

Increased Progastrin-Releasing Peptide Expression is Associated with Progression in Gastric Cancer Patients.

PurposeThe purpose of this study was to assess the diagnostic and prognostic value of serum progastrin-releasing peptide (ProGRP) in patients with gastric cancer (GC).Materials and MethodsA total of 150 patients with GC (89 males and 61 females) were recruited, including those with stage I (n=28), stage II (n=33), stage III (n=50), and stage IV (n=39) disease; 50 healthy controls and 66 patients with benign gastric diseases were also enrolled. Levels of serum ProGRP, carcinoembryonic antigen (CEA), and carbohydrate antigen 72-4 (CA72-4) were measured in all subjects.ResultsSerum ProGRP levels were significantly higher in GC patients than in controls (p<0.001), and ProGRP was significantly correlated with tumor size, tumor node metastasis stage, differentiation, invasion depth, and lymph node metastasis (p< 0.005). ProGRP levels were significantly decreased after chemotherapy (p<0.001). Receiver operating characteristic curves revealed a sensitivity and specificity for serum ProGRP in GC of 85.9% and 81.2%, respectively. ProGRP levels were positively correlated with CA72-4 and CEA (r=0.792 and 0.688, p<0.05, respectively). Combined detection of ProGRP, CEA, and CA72-4 showed the best diagnostic power for GC.ConclusionProGRP may be useful as a potential biomarker for GC diagnosis and therapy.

Pro-gastrin-releasing peptide as a marker for the Ewing sarcoma family of tumors

Pro-gastrin-releasing peptide (ProGRP) is an established tumor marker of small cell lung cancer. The purpose of this study was to determine if ProGRP could serve as a tumor marker for the Ewing sarcoma family of tumors (ESFTs). Sixteen patients with ESFTs (mean age 32years) were included in this study. As a control group, 42 patients with other tumor types that clinically or pathologically mimic ESFTs were also analyzed. Pre-treatment serum ProGRP and neuron-specific enolase (NSE) levels, the relationships between these levels, and tumor volume were investigated. In addition, serial changes in the serum or plasma ProGRP (6 patients) and NSE levels (5 patients) were measured over the course of treatment. Pre-treatment serum ProGRP levels were higher than the normal range in 8 of 16 patients; for these eight patients, ProGRP levels positively correlated with tumor volume (R = 0.99). In the control group, ProGRP levels were within the normal range, except for the two patients. Changes in ProGRP levels during treatment were consistent with tumor volume. Serum NSE levels were elevated in 14 of 16 patients with ESFTs and 8 of 42 patients with other tumor types. The range of NSE elevation was much smaller compared to that of ProGRP. Our data indicate that ProGRP is superior to NSE in terms of specificity. Serum ProGRP levels were elevated in half of the patients with ESFTs and reflected therapeutic response. ProGRP is a reliable tumor marker for the diagnosis of ESFTs and evaluation of treatment response.

Application of magnetic resonance diffusion-weighted imaging combined with serum tumor markers in brain metastases of small cell lung cancer

Objective To investigate the value of magnetic resonance diffusion-weighted imaging (DWI) in combination with peripheral serum tumor markers in the diagnosis and therapeutic evaluation of small cell lung cancer (SCLC) brain metastases. Methods Retrospective analysis of 368 SCLC cases diagnosed by histopathology or cytology from February 2009 to February 2012 in Shanxi Provincial Cancer Hospital was made. All patients underwent pathological examination of progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE) and brain DWI, and measured the apparent diffusion coefficient (ADC) of DWI sequences of brain metastases. The difference between the positive rates of ProGRP and NSE in patients with or without brain metastases was compared by the χ 2 test, and the diagnostic efficiency of ProGRP, NSE, DWI and combined detection for brain metastases were analyzed. The Kruskal-Wallis H test was used to compare the changes of ADC value, ProGRP and NSE before and after brain irradiation therapy in brain metastases of SCLC. Pearson correlation analysis was made to evaluate the correlation between the changes of ADC value and the levels of ProGRP and NSE in SCLC patients with brain metastases before and after treatment. Results The median expression of serum ProGRP in 169 SCLC patients was 2 664.7 pg/ml (98.4-4 876.8 pg/ml), with a positive rate of 98.2% (166/169). The median expression of NSE was 41.9 μg/L(9.4-264.3 μg/L), with a positive rate of 70.4% (119/169). The median expression of serum ProGRP level was 514.3 pg/ml (3.9-2 899.3 pg/ml) in 199 SCLC patients without brain metastasis, the positive rate was 89.4% (178/199). The median expression of NSE was 40.4 μg/L (0.3-176.1 μg/L), with a positive rate of 64.8% (129/199). The difference of ProGRP level between the two groups was statistically significant (u = 121.47, P < 0.001), but there was no significant difference in NSE level (u = 1.35, P = 0.12). The sensitivities of ProGRP, NSE, DWI, ProGRP+DWI and NSE+DWI were 68.4%, 41.2%, 66.7%, 92.2%, and 82.4%, and the specificities were 52.9%, 35.3%, 76.5%, 94.1%, and 88.2%. The sensitivity and specificity of ProGRP+DWI and NSE+DWI were higher than those of single test, and the differences were statistically significant (all P < 0.001). One hundred and fifty-six SCLC patients with brain metastases were treated with whole brain radiotherapy. Pearson correlation analysis showed that ADC values were negatively correlated with ProGRP and NSE levels (r = -0.945, P < 0.001; r = -0.995, P < 0.001). Conclusion DWI combined with ProGRP and NSE can provide objective evidence and clinical guidance for the diagnosis of SCLC brain metastases and the evaluation of whole brain radiotherapy. Key words: Small-cell lung carcinoma; Brain metastases; Progastrin-releasing peptide; Neuron-specific enolase; Magnetic resonance imaging

Reference intervals for serum progastrin-releasing peptide in healthy Chinese adults with electrochemiluminescence immunoassay.

Reliable reference intervals for serum progastrin-releasing peptide (ProGRP) in healthy Chinese adults with electrochemiluminescence immunoassay (ECLIA) are still lacking in the Chinese population. The study aims to establish reference intervals for ProGRP with ECLIA in apparently healthy Chinese adults. A total of 384 apparently healthy individuals from six representative geographical regions in China were enrolled: 200 males and 184 females with a mean age of 43.4±12.2 years, and an age range from 21 to 85 years. Serum ProGRP levels were analyzed on Cobas e601 automatic immunoassay analyzer with ECLIA. Reference intervals for serum ProGRP with ECLIA were determined following CLSI C28-A3 guidelines using a nonparametric method. In an apparently healthy Chinese population, the reference intervals for serum ProGRP with ECLIA were ⩽53.92 ng/L for adults aged 21-70 years and ⩽75.69 ng/L for adults aged >70 years, respectively. The reference values for serum ProGRP with ECLIA in an apparently healthy Chinese population were established according to the CLSI C28-A3 document, providing a reference for the clinical work.

Imaging Somatostatin Receptor Activity in Neuroendocrine-differentiated Prostate Cancer

Neuroendocrine-differentiated prostate cancer (NEPC) is a rare pathophysiology. We herein report a patient diagnosed with conventional prostate adenocarcinoma before hormone therapy, which was later diagnosed as NEPC. The nadir of prostate-specific antigen (PSA) was achieved once. However, adenocarcinoma changed to NEPC in recurrence, and the serum progastrin-releasing peptide (Pro-GRP) and neuron-specific enolase (NSE) values increased. A prostate needle biopsy revealed neuroendocrine differentiation. The chemotherapy regimen was changed, and somatostatin receptor scintigraphy (SRS) helped to determine the distribution and features of lesions as well as the effects of therapy. When prostate cancer worsens despite conventional therapy, NEPC should be considered.

Choice of serum tumor markers in patients with small cell lung cancer: progastrin-releasing peptide, neuron-specific enolase, and carcinoembryonic antigen

Abstract Lung cancer is a leading cause of cancer-related deaths worldwide. It mainly consists of 2 histological types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC, including squamous cell carcinoma and adenocarcinoma). The present study aimed to assess the role of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) and their combinations in the histological diagnosis of lung cancer (specially SCLC), which is of great importance for the initiation of treatment and prognostic implications. Serum ProGRP, NSE, and CEA were determined by the electrochemiluminescence immunoassay (ECLIA) in 66 patients with SCLC, 73 with adenocarcinoma, 44 with squamous cell carcinoma, 45 with non-malignant pulmonary diseases, and 50 healthy controls. Receiver operating characteristic curves were constructed to compare the predictive ability of each biochemical marker and their combined detection models to discriminate among the patients with lung cancers of different histological groups, benign pulmonary diseases and healthy individuals. In the ECLIA detection system, ProGRP showed the sensitivity and specificity for SCLC diagnosis were 71.2% and 91.1% to 93.2%, respectively. Among the markers, the largest area under the ROCs was for ProGRP in discriminating SCLC from benign pulmonary diseases, squamous cell carcinoma and adenocarcinoma (0.815, 0.859, and 0.835, respectively), which indicated that ProGRP was the most efficient marker for identifying SCLC. Besides, ProGRP and NSE exhibited almost equivalent diagnostic performance in discriminating SCLC from benign diseases. As for squamous cell carcinoma, we recommended proGRP, while for adenocarcinoma, the combination of proGRP and CEA was preferred. Remarkably, when ProGRP ≤ 66 pg/mL, CEA was of great value in diagnosing SCLC and adenocarcinoma. If CEA ≤ 5 ng/mL, the patient was at higher risk for SCLC, whereas the patient was more likely to be diagnosed with adenocarcinoma. Our study provided promising information about the diagnostic values of serum ProGRP, NSE, CEA in distinguishing SCLC from benign pulmonary diseases and NSCLC, which was of crucial clinical significance in the early diagnosis and therapy of SCLC.

Age and Gender-Specific Reference Intervals for ProGRP in Healthy Chinese Han Ethnic Adults using the Roche Cobas Immunoassay.

Pro-gastrin-releasing peptide (ProGRP) is a kind of tumor marker applied more and more commonly in recent years. This study was aimed at determining the age and gender-specific reference intervals (RIs) for ProGRP in healthy Han ethnic adults from Guangxi, China. A total of 2,045 apparently healthy males and 1,740 apparently healthy females aged from 21 to 90 years were included in this study. The serum ProGRP values were determined by electrochemiluminescence immunoassay (ECLIA). The one-sided upper 95th percentile of ProGRP concentrations were used to define the RIs. The reference limits in different age groups (21 - 40, 41 - 50, 51 - 60, 61 - 70, and > 70 years) were 37.3, 39.7, 45.7, 47.3, and 61.3 pg/mL for males, and 36.3, 38.1, 42.7, 53.5, and 60.1 pg/mL for females, respectively. There was no significant difference in the levels of ProGRP between males and females. The serum ProGRP levels were positively correlated with age. We established the age and gender-specific RIs for ProGRP in the adults from Guangxi, China. It will be valuable for future clinical and laboratory studies.