Serum Progastrin-releasing Peptide Research Articles

Clinical Application of Pro-Gastrin-Releasing Peptide.

The diagnostic sensitivity and specificity of serum Pro-gastrin-releasing peptide (ProGRP) in benign or malignant diseases remains controversial. The clinical data of 6,948 patients who were examined for ProGRP from February 2015 to January 2017 in the Zhongshan Hospital of the XiaMen University, were collected. The clinical data of the different groups were analyzed by statistical methods. The ProGRP reference levels were 68.50 pg/mL. The percentages of abnormal ProGRP levels were 23.87%, 26.14%, 22.87%, 84.56%, 16.1%, 15.59% and 43.75% for the pneumonia, cardiovascular disease, cerebral vascular disease, renal failure, small cell lung cancer (SCLC), colorectal cancer, and prostate cancer groups, respectively. The 95th percentile of the serum ProGRP concentration levels in the renal failure group was 364.22 pg/mL. The ProGRP cutoff levels for SCLC group were 162.90 pg/mL and the area under the receiver-operating characteristic curve (AUC) was 0.940 (95% CI, 0.892 to 0.987). The parameters sensitivity, specificity, PLR (positive likelihood ratio), NLR (negative likelihood) and Kappa value for the SCLC group with the exclusion of the renal failure group were 81.10% (95% CI: 38.19% - 89.71%), 99.51% (95% CI: 99.31% - 99.66%), 167.59 (95% CI: 116.06 - 241.99), 0.19 (95% CI: 0.11 - 0.32), and 0.6830 (Sig: 0.000), respectively. In the SCLC group, significantly higher concentrations of serum ProGRP of M1 were observed compared with M0. All esophageal neoplasms with high-level ProGRP were identified as small cell neoplasms. The ProGRP levels were increased in a variety of benign and malignant diseases and were considered a putative marker for SCLC with the exception of the renal failure group. It may be suggested that the high ProGRP levels originated from patients with neuroendocrine tumor.

Establishment of cut-off value of serum pro-gastrin-releasing peptide for diagnosis of small cell lung cancer and evaluation on the clinical diagnosis efficiency

Objective: To determine critical reference value (cut-off value) of serum pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase(NSE) in the diagnosis of small cell lung cancer(SCLC). To evaluate the clinical significance of serum levels of ProGRP and NSE in diagnosis and differential diagnosis in SCLC. Methods: Three hundred and fifty-two SCLC patients, 163 non small cell lung cancer(NSCLC)patients , 193 benign pulmonary disease patients and 140 healthy people visiting in National Cancer Hospital were analyzed retrospectively from January 2014 to July 2017.The levels of serum ProGRP and NSE of people were determined using electrochemiluminescent immunoassay respectively . Reference value ranges of the makers were determined by using the method of ROC curves. Results: In NSCLC group, benign lung disease group, healthy control group and mixed group (NSCLC+ lung benign diseases+ healthy control group) as a reference, the cut-off values were 58.3, 62.3, 57.8, 61.3 ng/L. In the diagnosis and differential diagnosis of SCLC and NSCLC, benign lung diseases, healthy controls and mixed group, AUC of ProGRP was 0.940 (0.919-0.961), 0.941 (0.921-0.960), 0.959 (0.944-0.975), 0.946 (0.928-0.963) respectively. The sensitivities of ProGRP were 86.4%, 84.9%, 86.4% and 84.7% respectively. The specificities of ProGRP were 95.7%, 96.9%, 99.3%, 98% respectively. In all groups the Youden's index of ProGRP and NSE were 0.821 vs 0.612, 0.818 vs 0.674, 0.857 vs 0.810, 0.827 vs 0.674. In healthy controls, no statistically significant difference was found between ProGRP and NSE (P>0.05) in the diagnosis of AUC. However, in the remaining 3 groups, the ProGRP diagnosis of AUC was significantly greater than that of NSE (P<0.01). Compared with single marker detection, the sensitivity of combined detection of ProGRP and NSE in diagnosis of SCLC increased to 95.5%, 94%, 96.6% and 94% in each group. There was no significant difference between ProGRP and ProGRP+ NSE in the diagnosis of AUC when compared with the NSCLC group and the mixed group (P>0.05). However, when combined with a healthy control group and a benign lung disease group, the ProGRP+ NSE combination was the highest for AUC diagnosis, compared with ProGRP and NSE (P<0.01). In the SCLC ED group serum ProGRP and NSE levels[776.33(3 103.4)ng/L, 52.14(60.59)μg/L]were higher than those in the SCLC LD group[295.59(799.65)ng/L, 23.36(22.97)μg/L], respectively (all P<0.001). The serum ProGRP levels of N0, N1, N2 and N3 in TNM staging were 113.0(343.65), 167.04(724.56), 427.42(1 388.62), 735.99(1 709.95)ng/L respectively (all P<0.001). Serum ProGRP and NSE levels were not statistically different between the sex groups and the age groups (all P>0.05). Conclusion: To establish the cut-off value of serum ProGRP is helpful for the diagnosis and differential diagnosis of SCLC.

Instability of Plasma and Serum Progastrin-Releasing Peptide During Repeated Freezing and Thawing

ObjectivesProgastrin-releasing peptide (proGRP) is a promising biomarker for small cell lung cancer. However, not much is known about how sample processing and storage conditions affect the stability of proGRP. Here, we examined the effects of repeated freeze–thaw cycles on the stability of proGRP in plasma and serum. MethodsConcentrations of proGRP were measured in plasma and serum samples exposed to two, three, or four freeze–thaw cycles and these were compared with values of corresponding samples exposed to one cycle (baseline). We also performed the area under the receiver-operating-characteristic curve (AUC) analysis to determine whether the differences of proGRP concentrations between each paired plasma and serum sample (ΔproGRP) can be used for identifying the samples that have been exposed to multiple freeze–thaw cycles. ResultsConcentrations of proGRP gradually decreased in both plasma and serum samples with increasing numbers of freeze–thaw cycles. Reduction rates of proGRP concentrations were greater in serum than in plasma samples and serum proGRP levels declined with statistical significance (p < 0.001) up to 10.1% after four freeze–thaw cycles. The ΔproGRP measurement showed fair accuracy (AUC = 0.741) for identifying samples that had been through four freeze–thaw cycles. The sensitivity was 82.8% and specificity was 62.1% at an optimal cut-off point of > 4.9. ConclusionOur study shows that the stability of circulating proGRP is affected in both plasma and serum samples by repeated freezing and thawing. We also show that ΔproGRP could be used for identifying paired plasma and serum samples subjected to multiple freeze–thaw cycles.

Overexpression of pro-gastrin releasing peptide promotes the cell proliferation and progression in small cell lung cancer

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.

Serum pro-gastrin-releasing peptide in diagnosis of small cell lung cancer: A meta-analysis.

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.

The diagnostic significance of single or combination lung cancer-related serum biomarkers in high risk lung cancer patients

The aim of this study was to assess the clinical value of pro-gastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCC-Ag), cytokeratin 19 fragment antigen 21-1(Cyfra21-1) and carcino-embryonic antigen (CEA ) in the diagnosis and clinical stage of lung cancer in Chinese patients. Patients with lung cancer and benign lesions confirmed by pathology were enrolled in Peking Union Medical College Hospital from January 2013 to October 2014. The serum levels of four tumor markers (ProGRP, SCC-Ag, Cyfra21-1 and CEA) were measured using immunoassays before treatment.The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the areas under the receiver operating characteristic curve (AUCROC) of these four tumor biomarkers were analyzed for the diagnosis of lung cancer. A total of 134 patients were finally analyzed, including 73 patients with lung cancer and the other 61 patients with benign lung disease.The diagnostic sensitivity of serum Cyfra21-1 to lung cancer was 67.1%, the specificity 45.1%, the AUCROC 0.658.The diagnostic sensitivity of the panel including ProGPR, Cyfra21-1 and CEA to lung cancer was 75.3%, the specificity 57.4%, the AUCROC 0.702. In the lung cancer group, the AUCROC of ProGRP over 65 ng/L to diagnose small cell lung cancer was 0.954; the AUCROC of SCC-Ag over 1.5 μg/L to diagnose squamous cell lung cancer was 0.788; the AUCROC of Cyfra21-1 to diagnose non-squamous-non-small-cell lung cancer was 0.716. In small cell lung cancer patients, the level of ProGRP in limited-disease small cell lung cancer (LD-SCLC) were significantly higher than that in extensive-disease small cell lung cancer (ED-SCLC) (P = 0.005). This panel of serum tumor markers including ProGRP, Cyfra21-1 and CEA improves the diagnostic specificity and sensitivity in patients with high-risk lung cancer. The serum CEA level of advanced lung cancer patients is significantly increased. The high level of serum ProGRP predicts the ED-SCLC.

The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer

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 13months. 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 >56ng/ml, a serum ProGRP level >58pg/ml, and a serum NSE level >19ng/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.

血清pro-GRP高値と縦隔リンパ節転移を示した肺定型的カルチノイドの1切除例

血清pro-GRP高値と縦隔リンパ節転移を示した肺定型的カルチノイドの1切除例

Correlations between serial pro-gastrin-releasing peptide and neuron-specific enolase levels, and the radiological response to treatment and survival of patients with small-cell lung cancer

IntroductionTo investigate whether decrease in the serum levels of pro-gastrin releasing peptide (ProGRP) and neuron-specific enolase (NSE) were correlated with the radiological response in patients with small-cell lung cancer (SCLC). MethodsOf the 196 patients, we retrospectively reviewed 118 patients elevated baseline levels of ProGRP and NSE prior to the initial therapy (IT) who survived for more than 1 month. The radiological response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). ResultsDecrease in the serum ProGRP was strongly correlated with the decrease of the sum of the tumor diameters (SOD) before the third course (ρ=0.50) and after the fourth course (ρ=0.42) of IT. Decrease in the serum NSE was weakly correlated with the decrease of the SOD after the fourth course (ρ=0.27), but not before the third courses (ρ=0.22). In the receiver operating characteristic (ROC) curves predicting 1-year survivors, the area under the curve (AUC) for percent changes in serum ProGRP before the third course were significantly larger than those for NSE (0.714 vs. 0.527, p=0.004). ConclusionsPercent changes in serum ProGRP showed better correlation to SOD and prognostic impact than that of NSE.

Clinicopathological findings of non-small-cell lung cancer with high serum progastrin-releasing peptide concentrations

Although progastrin-releasing peptide (proGRP) is used as a serum tumor marker for small cell lung cancer (SCLC), high serum pro-GRP concentrations are observed in some non-small-cell lung cancers (NSCLCs). The characteristics of these NSCLCs are not well known. To determine the clinicopathological features of NSCLC in patients with elevated serum proGRP concentrations, serum proGRP values were assessed in 654 advanced lung cancer patients, and positive (>46pg/mL) NSCLC specimens were subjected to cytological and histopathological reevaluation. Serum proGRP concentrations were positive in 34 of 421 NSCLC patients (8.1%) and 186 of 233 SCLC patients (80%). Histological subtypes of the 34 NSCLC patients at diagnosis were 20 adenocarcinomas, 5 squamous cell carcinomas, 4 large cell carcinomas, and 5 large cell neuroendocrine carcinomas. Six of 27 cytology specimens contained characteristic neuroendocrine morphology. Immunohistochemical analysis showed that 11 of 17 tumors were positive for neuroendocrine markers (64.7%). Twenty of 34 serum proGRP-positive NSCLC patients received platinum-based chemotherapy, and the response rate was 55.0%. These results suggest that serum proGRP-positive NSCLCs may have neuroendocrine differentiation. In addition, serum proGRP-positive NSCLCs may have clinical characteristics that are different from other NSCLCs.

Diagnostic value of ProGRP and NSE for small cell lung cancer: a meta-analysis

背景与目的胃泌素释放肽前体（pro-gastrin-releasing peptide, ProGRP）和神经元特异性烯醇化酶（neuron specific enolase, NSE）是目前研究较多的小细胞肺癌（small cell lung cancer, SCLC）肿瘤标记物，本研究综合评价了二者对SCLC的诊断价值。方法检索Pubmed、OVID、Elsevier Sciencedirect、Springer、Cochrane Library、Em-base、IFCC、中国生物医学文献数据库和维普医药信息资源系统，收集血清ProGRP与NSE用于SCLC诊断的研究数据。通过meta分析拟合SROC曲线，合并诊断效应量，比较ProGRP和NSE对SCLC的诊断效能。结果本次meta分析共纳入10篇文献，累计病例2 536例，其中SCLC 935例，非小细胞肺癌（non-small cell lung cancer, NSCLC）1 601例，对照849例。ProGRP和NSE的合并敏感度分别为0.70和0.61，合并特异度为0.93和0.90，合并阳性似然比为11.57和5.67，合并阴性似然比为0.32和0.45，合并诊断比值比为36.45和13.08。SROC曲线显示，ProGRP和NSE的Q*统计量分别为0.804 2和0.723 2，但差异无统计学意义。结论ProGRP对SCLC的鉴别能力与NSE相近，但特异度更高，可以作为SCLC的诊断指标。

Pulmonary Sequestration with Elevated Serum Level of Progastrin-releasing Peptide

A 74-year-old woman with rheumatoid arthritis was referred for a mass incidentally noted on chest radiograph. Chest CT scan showed cystic lesions in the right lower lobe. The lesion was evaluated as bronchiectasis, and she was followed up. Three years after the initial presentation, the appearance of the lesion had changed significantly and an elevated air-fluid level in the cystic structures was shown on chest CT scan. The preoperative serum progastrin-releasing peptide (proGRP) level was elevated (108.0 pg/ml; normal: <50 pg/ml). Histopathological specimen obtained by standard lower lobectomy confirmed that the lesion was an intralobar pulmonary sequestration. In the resected lobe, there was no malignant finding, but there were neuroendocrine tumorlet cells, which were positive for proGRP. One month after the resection, the serum proGRP level returned to normal. No pulmonary sequestration with high levels of proGRP has been reported, and this is the first case with elevated serum levels of proGRP.

The clinical value of vascular endothelial growth factor in patients with small cell lung cancer

It is well-known that vascular endothelial growth factor (VEGF) relates to the oncogenesis and development and metastasis of cancer, and patients with small cell lung cancer (SCLC) often have poor prognosis, earlier metastasis and shorter survival. This study is designed to investigate the effect of VEGF on the oncogenesis and development of SCLC and the clinical significance and prognostic value of VEGF in patients with SCLC. Serum VEGF level and pro-gastrin releasing peptide (ProGRP) level were measured using enzyme-linked immunosorbent assay (ELISA) in patients with SCLC before treatment and patients with benign lung diseases and in healthy persons, and serum neuron specific enolase (NSE) levels measured using radioimmunoassay. There were significant difference of serum VEGF level between the patients with SCLC and the patients with benign lung diseases and healthy persons (P < 0.05). Taking the mean concentration of serum VEGF as a cut-off, patients were divided into high VEGF (> 489.1 ng/L) and low VEGF (≤489.1 ng/L) groups, and the sensitivity and the specificity were 32.8% and 95.7% respectively. It was shown that the serum levels of VEGF in patients with SCLC didn't correlate with clinical features including age, gender, performance status and treatment, but correlated with disease staging (P < 0.05). High VEGF level was found more frequently in patients with extensive disease of SCLC than in those with limited disease (P < 0.05). The correlations weren't found between serum VEGF level and NSE level, ProGRP level in patients with SCLC (r=0.221, P > 0.05; r=0.217, P > 0.05). However, the positive rate of diagnosising SCLC was 54.1% by the determinant of serum VEGF allied serum NSE, 73.8% by the determinant of serum VEGF allied serum ProGRP and 78.7% by the determinant of serum VEGF allied se-rum NSE and serum Pro-GRP. Patients with high VEGF level had a significantly shorter overall survival time than those with low VEGF level in univariate survival analysis (P < 0.05). Further, the high VEGF level remained as a significantly determinant of poor survival in multivariate analysis (P < 0.05). There is a significant correlation between serum level of VEGF and survival in patients with SCLC. Serum VEGF may be regarded as a prognostic factor. The serum assay for VEGF using ELISA can be easily and repeatedly performed because of minimal invasiveness, hence serum VEGF measurement may be regarded as a subsidiary experiment of tumor marker in the patients with SCLC.

Serum progastrin‐releasing peptide levels followed by whole‐body positron emission tomography detects early recurrence of small‐cell lung cancer

A 65-year-old male smoker with severe COPD was diagnosed with limited-stage small-cell lung cancer. After receiving cisplatin/irinotecan, serum progastrin-releasing peptide (ProGRP) levels decreased to within the reference values and the lesions were markedly reduced in size. A whole-body 18F-fluorodeoxyglucose PET (FDG-PET) scan confirmed complete remission. During follow up, serum ProGRP levels increased, and a whole-body FDG-PET scan detected recurrence at the hilar lymph node that had been negative on CT. Complete remission was again achieved with second-line chemotherapy (cisplatin/etoposide) and local irradiation to the hilar lymph node. Monitoring serum ProGRP levels, followed by whole-body FDG-PET when indicated, may improve the clinical management of patients with small-cell lung cancer after initial complete remission.

EDITORIAL

EDITORIAL

Small-cell neuroendocrine carcinoma as a variant form of prostate cancer recurrence: A case report and short literature review

Background Small-cell neuroendocrine carcinoma has been recognized as a rare histologic variant occurring in only 0.5% to 2% of prostatic primary tumors. However, recent autopsy studies suggest development to this phenotype in up to 10% to 20% of the cases with hormone-refractory disease. Case Presentation A case of conventional adenocarcinoma before androgen-ablation therapy but showing progression to small-cell neuroendocrine carcinoma at the recurrence. The immunohistochemistry of the tumor showed strong positive staining for progastrin-releasing peptide (ProGRP), a carboxy terminal region common to 3 precursors for gastrin-releasing peptide, but almost negative staining for chromogranin-A and prostate-specific antigen. Combination chemotherapy based on cisplatin and etoposide was effective for controlling the tumor progression for 7 months, and the serum ProGRP level correlated well to the clinical course. Neither objective nor subjective responses were observed to somatostatin analogue therapy performed in the late stage of disease. Conclusions The present case reminds the urologist that small-cell neuroendocrine carcinoma may be a variant form of disease recurrence during androgen ablation in advanced prostate cancer. A strategic approach for this phenotype evaluating serum neuroendocrine markers, such as ProGRP, should be taken when serum prostate-specific antigen does not reflect the disease state. This approach would allow one to choose alternative therapies targeting neuroendocrine cells other than androgen ablation.

Study on the value of tumor markers ProGRP, CYFRA21-1, NSE and CEA in the differential diagnosis of pleural effusion

Malignant pleural effusion is usually caused by lung cancer, and tumor markers may be helpful to its differential diagnosis. The aim of this study is to explore the clinical value of serum and pleural effusion pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE), cyto- keratin fragment 19 (CYFRA21-1) and carcinoembryonic antigen (CEA) in differential diagnosis and histological typing of malignant pleural effusion caused by lung cancer. According to histological type of primary tumor, 99 patients with malignant pleural effusion caused by lung cancer were divided into small cell lung cancer (SCLC) group, adenocarcinoma group and squamous cell carcinoma group, with 37 patients with benign pleural effusion and 35 healthy persons as controls. Diagnostic value of serum and pleural effusion ProGRP , NSE, CYFRA21-1 and CEA was evaluated for each group. The levels of ProGRP, NSE, CYFRA21-1 and CEA in serum and pleural effusion of all the malignant groups were significantly higher than those in the control groups (P < 0.01). In the SCLC group, detection of pleural effusion ProGRP showed the highest Youden index and accuracy. In the adenocarcinoma group and squamous cell carcinoma group, combined detection of pleural effusion CEA+CYFRA21-1 (on parallel test) showed the highest Youden index and accuracy. Detection of pleural effusion tumor markers ProGRP, CYFRA21-1, NSE and CEA is of great clinical value in differential diagnosis and histological typing of malignant pleural effusion. Pleural effusion ProGRP is the optimal tumor marker for malignant pleural effusion caused by SCLC. Pleural effusion CEA+CYFRA21-1 (on parallel test) is a good auxiliary diagnosis index for malignant pleural effusion caused by adenocarcinoma and squamous cell carcinoma of the lung.

The Prognostic Significance of Circulating Neuroendocrine Markers Chromogranin A, Pro-Gastrin-Releasing Peptide and Neuron-Specific Enolase in Patients with Advanced Non-Small-Cell Lung Cancer

Background: Chromogranin A (CGA), Pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) are known as immunohistochemical tissue markers closely associated with neuroendocrine differentiation in non-small-cell lung carcinoma (NSCLC). The aim of the present study was to assess the value of serum levels of these markers in predicting response to chemotherapy and survival of patients with unresectable NSCLC. Methods: The study included 67 patients with advanced NSCLC treated with chemotherapy. Before treatment, serum levels of CGA, ProGRP and NSE were measured with commercial kits. Results: No association was found between serum NSE and age, gender, histology, performance status or extent of the disease. Distribution of serum CGA differed significantly according to gender and histology, with higher levels being found in men (p = 0.01) and in squamous cell carcinoma (p = 0.01). Serum ProGRP levels correlated with disease extent, being higher in patients with metastatic disease (M1) than in those with locoregional disease (M0; p = 0.02). The association of NSE, CGA and ProGRP levels with response to chemotherapy was not significant. While NSE had no impact on survival, the median survival was shorter for patients with elevated serum CGA and longer for patients with high ProGRP levels. Association with survival was significant when the Classification and Regression Tree (CART)-derived or median cutoff points were explored. On inclusion in multivariate Cox models, both CGA and ProGRP retained significance with high levels showing an opposite effect on survival [CART-derived cutoff points: CGA, relative risk (RR) –4.0; p < 0.001, and ProGRP, RR –0.4; p = 0.006, and median cutoff points: CGA, RR –1.8; p = 0.04, and ProGRP, RR –0.5; p = 0.03]. The combined use of CGA, ProGRP and NSE allowed for definition of two sets of patients with significantly different median survival times (25.2 vs. 8.8 months, p = 0.0001). Conclusions: In the circulation, CGA and Pro-GRP appear to bear important information related to the prognosis for NSCLC patients before chemotherapy. While a high CGA before treatment was found as an unfavorable prognostic determinant, a high ProGRP conferred a survival advantage. The combined use of serum CGA, ProGRP and NSE may supply additional information to prognosis.

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression.

A clinical study of ProGRP as a new tumor marker for small cell lung cancer

To evaluate the significance of progastrin-releasing peptide (ProGRP) as a new tumor marker for small cell lung cancer (SCLC).. Fifty-five patients with pathologically proved SCLC were initially treated and retrospectively studied, in which the level of serum ProGRP was tesed in various situations and its relationship with tumor stage and therapeutic effects was observed. The diagnostic sensitivity and specificity of ProGRP to SCLC were 80.0% and 97.0% respectively. The average ProGRP level in extensive disease of SCLC patients was 820.00 ng/L, significantly higher than 205.86 ng/L in limited disease of SCLC patients (P=0.000 3). In chemotherapy sensitive cases, the ProGRP level had a significant decrease after treatment, while there was no change in failure cases. ProGRP is a new SCLC tumor marker with high specificity and sensitivity. It has a close relationship with SCLC stage and can be used as a predictor of SCLC to chemotherapy response.