Serum ProGRP Research Articles

A fluorescence-based lateral flow immunoassay using AIEgen-encapsulated nanoparticles to rapidly and sensitively detect pro-gastrin-releasing peptide.

Afluorescence lateral flow immunoassay (F-LFIA) is presentedusing nanoparticles with encapsulated molecules whose emission is caused by aggregation as the fluorescent label to quantitatively detect gastrin-releasing peptide precursor(proGRP) in serum. The detection system was optimized to achieve a broad linear detection range of 10 ~ 5000 pg/mL and a detection limit of 6 pg/mL for F-LFIA. The proposed method exhibited good sensitivity, specificity, and reproducibility. The performance and applicability of the F-LFIA were evaluated in the analysisof 183 human serum samples, and the results were strongly correlated with those of the electrochemiluminescence immunoassay. The proposed F-LFIA can serve as a precise and rapid detection method to detect proGRP and has potential for the early diagnosis of small-cell lung cancer (SCLC).

Assessment of Progastrin Releasing Peptide in Gastric Cancer Patients

Abstract Background Gastric cancer is the 3rd cause of cancer related deaths and fifth most common malignant tumor worldwide. It`s prevalence is increasing in conjunction with H.Pylori infection, smoking, alcohol consumption, bad nutritional habits (smoked food, food rich in salt and nitrites, processed meat), obesity, genetic predisposition. Aim of the Work To investigate associations among serum ProGRP levels and clinicopathological parameters, and to evaluate the diagnostic value of serum ProGRP for GC. Patients and Methods The current study was conducted at Damietta cardiology and gastroenterology center in association with Ain Shams University Hospitals aiming to elucidate the diagnostic value of serum progastrin releasing peptide in patients with gastric cancer. A total of 75 subjects were enrolled in the current study, and they were divided into three equal groups; the first one included 25 healthy controls, the second one included 25 patients with benign gastric lesions, while the third one included 25 patients with malignant gastric lesions. Results Our study showed the following findings: CEA had sensitivity and specifity of 64% and 60 % for differentiating between benign and malignant group which means low diagnostic ability of CEA in detecting gastric cancer. Progastrin Releasing peptide (Pro GRP) had 96% sensitivity and 96% specifity in differentiating between benign and malignant groups which means higher diagnostic abilities of Pro GRP in cancer stomach. Conclusion Based on thde previous findings we recommend: Use of progastrin Releasing peptide (PRP) as screening marker for patients suspected to have gastric cancer as it has been proved to higher diagnostic abilities than CEA. Evaluate PRP role in monitoring for tumor staging and prognostis.

Detection of Changes in CEA and ProGRP Levels in BALF of Patients with Peripheral Lung Cancer and the Relationship with CT Signs.

To investigate the relationship between the detection of changes in the levels of carcinoembryonic antigen (CEA) and progastrin-releasing peptide (ProGRP) in bronchoalveolar lavage fluid (BALF) and CT signs in patients with peripheral lung cancer. Retrospective analysis of 108 patients with perihilar lung cancer who attended our hospital from January 2019 to January 2022, 54 cases were randomly selected as the observation group and 50 cases as the control group. Patients in both groups received CT examination and BALF test at the same time to observe and compare the differences in serum levels, the relationship between CT signs and serum indices, and the diagnostic value of peripheral lung cancer between the two groups. The serum levels of ProGrp, CEA, CA211, and NSE in the observation group were significantly higher than those in the control group, and the difference was statistically significant (P < 0.05). The morphology, density, mass enhancement pattern, bronchial morphology, obstructive signs, and lymph node fusion of CT signs were compared between the observation group and the control group, indicating that CT signs were more helpful for the localization, diagnosis, and staging of lung cancer. The results of ROC curve analysis showed that the AUC value of low-dose CT combined with serum ProGrp, CEA, CA211, and NSE was 0.892, sensitivity was 96.21%, and specificity of 90.05%, which were significantly higher than those of the single tests, respectively. The positive likelihood ratio was 84.41% and the negative likelihood ratio was 87.11%. The combination of CT signs and serum tumour markers helps to improve the detection rate, sensitivity, and specificity of lung cancer, which has a high diagnostic rate for lung cancer and may provide evidence for the early diagnosis of lung cancer.

Changes in lung cancer-related serum tumor markers in patients with chronic kidney disease and determination of upper reference limit.

To investigate the changes in lung cancer-related serum tumor markers in patients with chronic kidney disease (CKD) and determine the upper reference limit for patients with different stages. Included inpatients diagnosed with CKD who did not receive dialysis temporarily in our hospital from March to September 2020. Changes in serum CA125, HE4, CYFRA21-1, SCCA, NSE and ProGRP in CKD patients were analyzed. The non-parametric method was used to estimate the upper reference limit of the above indicators in patients with CKD stages 2-5. The serum levels of HE4, CYFRA21-1, SCCA, and ProGRP in the CKD group were significantly higher than those in the healthy control group; CA125 and NSE levels were not statistically different. The false positives of SCC, CYFRA21-1, ProGRP, and HE4 increased significantly with the CKD stage. Still, NSE and CA125 did not show a significant increasing trend. Both HE4 and ProGRP have independent upper reference limits from CKD2 to CKD5 stage, namely 220.8 pmol/l and 101.4 pg/ml in the CKD2 stage, 496.7 pmol/l and 168.63 pg/ml in CKD3 stage, 4592.4 pmol/l and 272.8 pmol/l for CKD4 stage, CKD5 stage was 4778.2 pmol/l and 491.6 pmol/l. This study preliminarily determined the upper reference limits of Lung cancer-related tumor markers in patients with different CKD stages and provided laboratory support for the rational use and interpretation of Lung cancer-related tumor markers in special populations.

Afatinib Targeted Therapy Affects the Immune Function and Serum Levels of EGFR and Gastrin-Releasing Peptide Precursor (pro-GRP) in Patients with Non-Small-Cell Lung Cancer (NSCLC).

Objective This study is aimed at investigating the clinical intervention effect of afatinib targeted therapy in patients with non-small-cell lung cancer. Methods The research object was a retrospective analysis of 86 patients with non-small-cell lung cancer who were admitted to our hospital from 1st January 2019 to 31st December 2021. The patients were divided into two groups. The patients in the two groups received conventional chemotherapy intervention, and the patients in group B received afatinib targeted therapy intervention on the basis of the treatment in group A. The clinical intervention effect, immune function, serum EGFR level, serum pro-GRP level, and incidence of adverse reactions were compared between the two groups of patients. Results After afatinib targeted therapy intervention, the total intervention effective rate of patients in treatment group B was significantly higher than that in patients in treatment group A. Compared with the treatment group A, the CD3+, CD4+, CD8+, and CD4+/CD8+ of the treatment group were significantly upregulated. After the intervention, the serum EGFR levels of patients in treatment groups A and B were significantly decreased, and the serum EGFR levels in patients in treatment group B were significantly lower than those in patients in treatment group A. The serum pro-GRP level in group B patients was significantly decreased. The overall incidence of adverse reactions in treatment group B was significantly lower than that in treatment group A. Conclusion Afatinib targeted therapy has a significant clinical intervention effect on patients with non-small-cell lung cancer, which not only helps to improve the immune function of patients but also effectively improves the serum EGFR and pro-GRP levels of patients.

Serum Cystatin, Chemokine, and Gastrin-Releasing Peptide Precursors and Their Clinical Value in Patients with Chronic Renal Failure.

Objective To investigate the serum cystatin (CysC), Chemerin, and gastrin-releasing peptide precursor (ProGRP) levels in patients with chronic renal failure (CRF). Methods CRF patients admitted to our hospital from February 2019 to July 2019 were selected as the observation group, and 50 healthy patients were selected as the control group. The serum levels of CysC, Chemerin, ProGRP, and Scr of all subjects were detected. Patients with CRF were admitted for peritoneal dialysis (PD) treatment for 1 week, and continued treatment was performed. The survival rate of patients with CRF in nearly 1 year after continuous treatment was observed. Multivariate analysis of factors affecting survival time of CRF patients undergoing peritoneal dialysis was performed. The results were compared with those in the health group. The expression levels of CysC, Chemerin, ProGRP, and Scr in the observation group were all decreased, and the differences were statistically significant (P < 0.05). Pearson correlation analysis showed that Scr expression in CRF patients is positively correlated with CysC, Chemerin, and ProGRP (P < 0.001). The survival rate of 98 patients with CRF was 80.61% (79/98), and the mortality rate was 19.39% (19/98). Serum levels of CysC, Chemerin, ProGRP, and Scr in the death group are all higher than those in the survival group, and the differences are statistically significant (P < 0.05). CysC, Chemerin, ProGRP, and Scr are independent risk factors affecting survival time (P < 0.05). The AUC aspects of serum CysC, Chemerin, ProGRP, and Scr in predicting the survival rate of CRF patients in the treatment phase are 0.840, 0.775, 0.782, and 0.725, respectively. Conclusion The serum levels of CysC, Chemerin, and ProGRP of CRF patients are abnormally elevated and are positively correlated with serum Scr of patients, which can be used as a reliable indicator of pathogenesis and prognosis assessment of CRF patients.

Circulating progastrin-releasing peptide in the diagnosis of Small Cell Lung Cancer (SCLC) and in therapeutic monitoring

Introduction: Progastrin-releasing peptide (proGRP), a precursor of GRP, has been recently reported as a putative circulating biomarker for differential diagnosis between non–small cell lung cancer (NSCLC) and SCLC. We evaluated the diagnostic effectiveness of proGRP to differentiate patients with NSCLC and SCLC and the usefulness of combined measurement of proGRP and neuron-specific enolase (NSE) for diagnosing SCLC.&#x0D; Methods: Serum proGRP, NSE, cytokeratin 19 fragment 21-1 (CYFRA 21.1), squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA) were prospectively collected and measured in patients with a new diagnosis of lung cancer. Serum proGRP was also measured in healthy subjects. The serum proGRP, NSE, CYFRA 21.1 and CEA concentrations were determined by an electrochemiluminescence immunoassay and the serum SCC Ag concentration was determined by an automated immunofluorescence assay. Differences between proGRP and NSE in patients with SCLC and NSCLC were evaluated and compared using Mann-Whitney test.&#x0D; Results: A total of 77 patients affected by SCLC (n = 17) and NSCLC (n = 60) were enrolled in the present study. Moreover, 50 cases of healthy subjects were analyzed for proGRP. SCLC patients showed a significantly higher proGRP (1,484 pg/mL; range 168-3,777) levels compared to NSCLC patients (45 pg/mL; range 31.7-60.6), p&lt;0.0001. In healthy subjects the median proGRP level was 36.1 (28.8-43.5) pg/mL, significantly lower than SCLC patients. ProGRP showed a higher specificity when compared to NSE, with a difference in proportion of 47.5% (95% confidence interval 32.5% to 62.5%, p&lt;0.001). Serial measurements of proGRP in SCLC patients showed a decrease in responsive chemotherapy patients.

A Case of Ewing’s Sarcoma Arising in the Cervical Spine with an Elevation of Serum ProGRP

We experienced a case of small, round-cell malignant neoplasm diagnosed by touch smear cytology and histopathology when an open biopsy was performed in a 50-year-old Japanese woman. She was suspected of having a cervical spine tumor after surgery for cervical spine foraminal stenosis. After consent, the cervical spine tumor histologically diagnosed by an open biopsy was confirmed to be Ewing sarcoma (EWS) by genetic testing. EWS belongs to a group of small, round-cell tumors that are morphologically similar and often difficult to differentiate. After the open biopsy, the present patient received radiotherapy, and her plasma level of Pro-Gastrin-Releasing-Peptide was decreased (217.2 pg/ml before surgery to 30.3 pg/ml; reference value: 0 - 80 pg/ml). We herein report the process for making the final diagnosis by focusing on the intraoperative cytology, histopathology, and immunohistochemical findings. Our diagnosis was validated by karyotyping and a fluorescence in-situ hybridization analysis.

Diagnostic Value and Clinical Significance of Combined Detection of Serum Markers CYFRA21-1, SCC Ag, NSE, CEA and ProGRP in Non-Small Cell Lung Carcinoma.

The aim of the study is to explore the diagnostic value and clinical significance of combined detection of serum markers CYFRA21-1, SCC Ag, NSE, CEA and ProGRP in non-small cell lung cancer. CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP levels of 113 patients with lung cancer, 110 patients with benign lung diseases, and 90 healthy volunteers were detected by electrochemiluminescence assay. The correlations between positive expressions and clinical and pathological parameters were analyzed. The diagnostic values of CYFRA21-1, SCC, NSE, CEA, and ProGRP were evaluated by plotting ROC curves. The positive expression rates of CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP in the lung cancer group significantly exceeded those of benign lung disease and healthy groups (p < 0.05). In the lung cancer group, CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP levels significantly varied in patients with different degrees of invasion and clinical stages in the presence/absence of lymph node metastasis (p < 0.05). AUCs of diagnosis by CYFRA21-1, ProGRP, CEA, SCC Ag, and NSE were 0.737 [95% CI (0.582 - 0.893)], 0.829 [95% CI (0.742 - 0.915)], 0.848 [95% CI (0.739 - 0.956)], 0.758 [95% CI (0.642 - 0.874)], and 0.857 [95% CI (0.764 - 0.951)], respectively, with the optimal cutoff values of 11.38 µg/mL, 103.47 pg/mL, 5.78 ng/mL, 3.92 ng/mL, and 13.36 ng/mL, respectively. The combined diagnostic sensitivity and accuracy both exceeded those based on individual markers, but the combined diagnostic specificity was slightly lower than those using CYFRA21-1, SCC Ag, and ProGRP alone. CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP levels of patients with lung cancer increased abnormally. The combined detection effectively improved diagnostic accuracy and sensitivity.

Selective Fishing for Peptides with Antibody-Immobilized Acrylate Monoliths, Coupled Online with NanoLC-MS.

An online microfluidics-mass spectrometry platform was developed for determining proteotypic peptides from in-solution digested samples. Accelerated and selective sample cleanup was achieved by integrating proteotypic epitope peptide immunoextraction with nano liquid chromatography-tandem mass spectrometry (online IE-nanoLC-MS/MS). Ten individually prepared 180 μm inner diameter capillaries with ethylene glycol dimethacrylate- co-vinyl azlactone (EDMA- co-VDM) monoliths were immobilized with anti-protein antibodies that are used in routine immunoassays of the intact small cell lung cancer biomarker ProGRP. The resulting AB columns provided linearity correlation coefficients of 0.96-0.99 for protein amounts and concentrations of 10 pg to 5 ng and 0.5-250 ng/mL, respectively. The columns/platform gave relative peak area RSDs below 15%. The IE-nanoLC-MS/MS platform provided a limit of detection (LOD) of 520 pg/mL of ProGRP in human serum. The approach was applicable for other matrixes and proteins, i.e., primary glioblastoma cells and endogenous αV integrin chain. Thus, EDMA- co-VDM monoliths immobilized with antibodies are suited for automated peptide capture in microfluidic formats.

Serum ProGRP and NSE levels predicting small cell lung cancer transformation in a patient with ALK rearrangement-positive non-small cell lung cancer: A case report.

The resistance mechanisms to anaplastic lymphoma kinase (ALK) inhibitors comprise ALK gene variations, such as ALK point mutations and copy-number gains, the activation of bypass signaling through the activation of other oncogenes and small cell lung cancer (SCLC) transformation. To date, few studies have investigated whether tumor markers for SCLC correlate with the SCLC transformation in EGFR-mutant NSCLC and ALK-positive non-SCLC (NSCLC). The present case study reported a patient with SCLC transformation after alectinib treatment. The patient exhibited elevation of pro-gastrin-releasing peptide precursor and neuron-specific enolase levels, which may be predictive of SCLC transformation during the resistance to ALK-tyrosine kinase inhibitors.

Establishment of the reference interval for serum pro-gastrin-releasing peptide in healthy adults of Chinese Han ethnicity.

The aim of this study is to establish the reference interval for serum pro-gastrin-releasing peptide (proGRP) determined by electrochemiluminescence immunoassay (ECLIA) in healthy Chinese Han ethnic adults. After screening, 9932 healthy Chinese Han adults (age range 18-95 years) were enrolled in this study, including 6220 men and 3712 women. Serum proGRP levels were measured by ECLIA. The reference interval was defined by non-parametric 95th percentile interval. Serum proGRP levels conformed to a non-Gussian distribution. The reference interval for healthy Chinese Han adults calculated by the non-parametric method was 0-73.90 ng/mL in this study. Since serum proGRP levels were significantly correlated with age (r=0.226, P<0.001), the participants were divided into six age groups: 18-39, 40-49, 50-59, 60-69, 70-79, and ⩾80 years. No significant difference for serum proGRP levels was found between the sexes at each of six age groups. The reference intervals were gradually increased with age (65.35 ng/mL, 68.65 ng/mL, 74.10 ng/mL, 77.65 ng/mL, 84.57 ng/mL, and 98.03 ng/mL in 18-39, 40-49, 50-59, 60-69, 70-79, and ⩾80 years, respectively). We established the reference interval for serum proGRP, which was determined by ECLIA in the healthy Chinese Han population. Furthermore, our study suggests that it is necessary to establish the age-specific reference intervals for serum proGRP.

Pro-Gastrin Releasing Peptide: A New Serum Marker for Endometrioid Adenocarcinoma

Background: Gastrin-releasing peptide (GRP) is thought to play a role in the metastatic process of various malignancies. The more stable precursor of GRP, pro-GRP (ProGRP), has been shown to be secreted by neuroendocrine tumors. This study was designed to assess the validity of ProGRP as a diagnostic marker in endometrioid adenocarcinomas (EAs) of the endometrium. Methods: Thirty-seven patients with a diagnosis of EA, 23 patients with endometrial hyperplasia, and 32 age-matched controls with normal endometrial histology were recruited for this study. Serum ProGRP and cancer antigen 125 (CA125) values were compared between groups. Results: Median serum ProGRP levels were significantly higher in the cancer group compared to corresponding levels in both the hyperplasia and control groups (p = 0.008 and p < 0.001 respectively; endometrial cancer: 27.5 pg/mL; hyperplasia: 16.1 pg/mL; controls: 12.9 pg/mL). Age and endometrial thickness were positively correlated with ProGRP levels (r = 0.322, p = 0.006 and r = 0.269, p = 0.023, respectively). Receiver Operating Characteristic curve analyses for EA revealed a threshold of 20.81 pg/mL, with a sensitivity of 60.7% and specificity of 81.4%, positive predictive value of 68% and negative predictive value of 76.1%. Conclusion: Significantly higher ProGRP levels were observed in patients with EA than in controls. Serum ProGRP has good diagnostic sensitivity and specificity for EA.

Clinical implications for pro-GRP in small cell lung cancer. A single center experience.

Recently, pro-gastrin-releasing peptide (pro-GRP) became available as an alternative sensitive, specific and reliable tumor marker for patients with small cell lung cancer (SCLC), both in limited (LD) and diffuse disease (DD). We retrospectively analyzed pro-GRP, neuron-specific enolase (NSE) and CEA in patients with SCLC and non-small cell lung cancer (NSCLC). Serum pro-GRP level was measured with electrochemiluminescence at our laboratory (cutoff 77.8 pg/mL). Continuous variables were analyzed with the Mann-Whitney test, contingency data with Fisher's exact test. Receiver operator characteristic (ROC) curve analysis was performed to identify threshold values to set the highest sensitivity (Sn) and specificity (Sp) values. A total of 65 patients were studied (49 men, median age 67 years, range 27-79). Thirty-seven patients had SCLC (29 DD, 8 LD) and 28 advanced NSCLC. Median pro-GRP level was 919 pg/mL (range 22-147,350) in SCLC and 32 pg/mL (range 10-119.2) in NSCLC (p<0.0001). NSE was 4.38-fold higher in SCLC patients (p = 0.0005); CEA did not reveal significant differences between groups. Pro-GRP Sn and Sp were 86.4% and 96.4%, respectively. With ROC curve analysis, a cutoff value of 329.3 pg/mL showed a Sn of 75.8% and Sp of 87.5% in discriminating DD from LD. Pro-GRP was not influenced by either liver metastases or renal impairment. Pro-GRP is sensitive for SCLC diagnosis. Since high marker levels are related to high disease burden, pro-GRP may have a negative prognostic significance. Follow-up studies are required to define its role in clinical practice in monitoring responses to treatment and early relapses.

Meta-Analysis of Serum Gastrin-Releasing Peptide Precursor as a Biomarker for Diagnosis of Small Cell Lung Cancer

Background:The serum level of gastrin-releasing peptide precursor (proGRP) is generally? elevated in patients with small cell lung cancer (SCLC). However, the diagnostic sensitivity and specificity of serum proGRP in SCLC cases remains controversial. The study aimed to assess the diagnostic value of this biomarker by meta-analysis.Materials and Methods:The Cochrane, Clinical trials, Pubmed, Web of Science and Embase databases were searched and diagnostic values were calculated or extracted. Statistical analysis was accomplished with RevMan 5.3 and STATA 12.0 software.Results:A total of 27 studies with 7268 participants were included. The pooled sensitivity, specificity, PLR, NLR and DOR were 0.754 (95% CI: 0.700-0.802), 0.945 (95% CI: 0.916-0.965), 13.804 (95% CI: 9.096-20.948), 0.260 (95% CI: 0.213-0.317) and 53.101 (95% CI: 34.327-82.145) respectively. The AUC was 0.910 (95% CI: 0.880-0.930). Significant publication bias was not found (P =0.622).Conclusions:The meta-analysis indicated that serum proGRP is indeed a useful biomarker with goodsensitivity and high specificity for diagnosis of SCLC. Therefore proGRP can be expected to be widely applied in the clinic for identification of lung cancer patients.

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.

Abstract 4704: The evaluation of INCB059872, an FAD-directed inhibitor of LSD1, in preclinical models of human small cell lung cancer

Abstract Methylated histone marks on H3K4 and H3K9 are generally coupled with transcriptional activation and repression, respectively. Altered levels of these histone methylation marks lead to abnormal gene expression and are associated with oncogenesis. Lysine specific demethylase 1 (LSD1) catalyzes demethylation of mono and di-methylated lysine 4 and 9 of histone H3 via an FAD-dependent redox-process. Deregulated LSD1 activity perturbs normal gene expression and can lead to cellular transformation. In particular, the function of LSD1 has been reported to maintain stem cell-like gene expression patterns in various cancers, most notably small cell lung cancer (SCLC), a cancer type that is characterized by a highly undifferentiated state and with high unmet medical need. INCB059872 is a potent, selective and orally bioavailable inhibitor of LSD1 that achieves inhibitory activity through the formation of covalent FAD-adducts. The effect of INCB059872 in SCLC cell lines was assessed in vitro and in vivo. In these studies, the proliferation of a panel of SCLC cell lines was inhibited by INCB059872, with EC50 values ranging from 47 to 377 nM. Non-tumorigenic cells, such as IL-2 stimulated T cells from normal donors, by contrast, were significantly less sensitive with IC50 values &amp;gt; 10 μM. Oral administration of INCB059872 on once daily (QD) and alternative day (QoD) dosing regimens inhibited tumor growth in the NCI-H526 and NCI-H1417 human SCLC xenograft models. Consistent with previous reports, INCB059872 treatment in these models led to the induction of the FEZ1 and UMODL1 genes relative to vehicle-treated animals, as part of a gene signature in SCLC cell lines that is predictive of LSD1 responsiveness. Moreover, serum levels of the neuroendocrine marker pro-GRP were markedly reduced at all efficacious dosing regimens in the NCI-H1417 human SCLC xenograft model, suggesting that serum pro-GRP levels could be used as a surrogate pharmacodynamic marker of LSD1 inhibition. Currently, the efficacy of INCB059872 in combination with standard of care therapies for SCLC is under evaluation in these preclinical models. These data support the clinical evaluation of INCB059872 in patients with SCLC. Citation Format: Sang Hyun Lee, Xuesong Mike Liu, Melody Diamond, Valerie Dostalik, Margaret Favata, Chunhong He, Liangxing Wu, Richard Wynn, Wenqing Yao, Gregory Hollis, Reid Huber, Peggy Scherle, Bruce Ruggeri. The evaluation of INCB059872, an FAD-directed inhibitor of LSD1, in preclinical models of human small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4704.

Pro-gastrin-releasing peptide and neuron-specific enolase: useful predictors of response to chemotherapy and survival in patients with small cell lung cancer.

The aim of this study was (1) to evaluate and predict the value of ProGRP and NSE in therapy and survival; (2) as well as to investigate the correlation between the ProGRP mRNA expression in peripheral blood and serum ProGRP protein. The study included 122 patients with SCLC without prior therapy. The serum levels of ProGRP and NSE were detected by enzyme-linked immunosorbent assay and eletro-chemiluminescence immunoassay, respectively. The expression of ProGRP mRNA was detected by real-time reverse transcriptase-polymerase chain reaction. Distribution of serum levels of ProGRP, NSE and ProGRP mRNA differed significantly according to tumor size, disease stage and distant metastasis (all P<0.05), and no association was found between them and gender or age (both P>0.05). After two courses of chemotherapy, patients of remission and stable groups showed a marked decrease in ProGRP and NSE concentrations (P<0.05). The ProGRP concentration of patients in progression group was significantly higher than pretreatment level (P<0.05), while NSE concentration was not. A linear nonparametric (Spearman) correlation test revealed that there was a significant correlation between ProGRP mRNA expression in peripheral blood and serum ProGRP protein level (P<0.05). Univariate analysis found a statistically significant association of survival with disease stage, distant metastasis, ProGRP and NSE (P<0.05). Gender, age and tumor size were not prognostic factors (P>0.05). Multiple Cox regression model analysis found that only disease stage and NSE were significant predictors (P<0.05). This study has found that there is a potential role for ProGRP and NSE in both therapy monitoring and predicting survival in SCLC patients.

Serum human epididymis protein 4 (HE4) may be a better tumor marker in early lung cancer

BackgroundHuman epididymis protein 4 (HE4) had been shown to be an ideal biomarker in ovarian cancer. However, there were fewer reports on its application in lung cancer. We explored the diagnostic value of serum HE4 as a biomarker in early lung cancer by comparing it with other biomarkers. Methods162 individuals including 112 cases of lung cancer at early stage and 50 healthy people as controls were enrolled. The serum concentrations of biomarkers were determined with the Roche Elecsys assays. ResultsIn comparison to the other biomarkers such as carcinoembryonic antigen (CEA), neuron-specific-enolase (NSE), serum cytokeratin 19 fragment (CYFRA 21-1) and progastrinreleasing peptide (proGRP), serum HE4 was one of the biomarkers with the highest sensitivity (43.8%) and specificity (95.0%) for early lung cancer diagnosis. In terms of histological results, serum HE4 was the best biomarker both in adenocarcinoma (AC) and squamous carcinoma (SC), and serum proGRP was the best in small cell lung cancer (SCLC). The combination of proGRP, NSE and HE4 could determine the histological type of lung cancer with a very high accuracy of 93.8%. ConclusionsThese findings suggested that serum HE4 was a better biomarker in early lung cancer than other frequently-used biomarkers.

ProGRP高値を示した非定型肺カルチノイドの1例

ProGRP高値を示した非定型肺カルチノイドの1例