proGRP Levels Research Articles

A comparative study of ProGRP and CEA as serological markers in small cell lung cancer treatment

BackgroundSmall Cell Lung Cancer (SCLC) presents a significant clinical challenge due to its aggressive nature and the need for effective biomarkers for treatment monitoring. This study aimed to compare ProGRP and CEA as serological markers in the monitoring of SCLC treatment.MethodsWe retrospectively analyzed data from 80 SCLC patients and 80 matched controls. ProGRP and CEA levels were measured, and their associations with clinical parameters, including tumor stage and treatment response, were assessed using Spearman’s rank correlation coefficient. Multivariate logistic regression models were employed to identify independent predictors of treatment response and disease progression.ResultsProGRP and CEA levels were considerably higher in cases than controls, with median ProGRP levels at 198.5 pg/mL versus 48.7 pg/mL and median CEA levels at 5.2 ng/mL versus 2.9 ng/mL (both p < 0.001). ProGRP levels correlated positively with tumor stage (ρ = 0.58, p < 0.001) and negatively with treatment response (ρ = − 0.45, p = 0.001). CEA levels also showed positive correlation with tumor stage (ρ = 0.48, p = 0.002) and negative correlation with treatment response (ρ = − 0.35, p = 0.005). Multivariate analysis revealed that ProGRP was an independent predictor for treatment response (OR 1.25 per 100 pg/mL increase, p = 0.001) and disease progression (OR 1.25 per 50 pg/mL increase, p = 0.012), while CEA was a marginal predictor for treatment response (OR 0.95 per 1 ng/mL increase, p = 0.045).ConclusionBoth ProGRP and CEA are significant serological markers in SCLC patients, with ProGRP showing a stronger correlation with tumor stage and treatment response. ProGRP may serve as a superior independent predictor of treatment response and disease progression compared to CEA. These findings support the incorporation of ProGRP in SCLC treatment monitoring protocols.

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.

Pleural pro-gastrin releasing peptide is a potential diagnostic marker for malignant pleural effusion induced by small-cell lung cancer.

Serum pro-gastrin releasing peptide (proGRP) is a well-recognized diagnostic marker for small cell lung cancer (SCLC). Pleural effusion is common in patients with advanced SCLC. The diagnostic accuracy of pleural proGRP for malignant pleural effusion (MPE) has not yet been established. This study aimed to evaluate the diagnostic accuracy of pleural proGRP for MPE. We prospectively recruited patients with undiagnosed pleural effusions from two centers (Hohhot and Changshu). An electrochemiluminescence immunoassay was used to detect pleural fluid proGRP. The diagnostic accuracy of proGRP for MPE was evaluated using a receiver operating characteristic (ROC) curve. In both the Hohhot (n=153) and Changshu (n=58) cohorts, pleural proGRP in MPE patients did not significantly differ from that in patients with benign pleural effusions (BPEs) (Hohhot, P=0.91; Changshu, P=0.12). In the Hohhot and Changshu cohorts, the areas under the curves (AUCs) of proGRP were 0.51 [95% confidence interval (CI): 0.41-0.60] and 0.62 (95% CI: 0.47-0.77), respectively. However, patients with SCLC-induced MPE had significantly higher proGRP levels than those with BPE and other types of MPE (P=0.001 for both). In the pooled cohort, the AUC of proGRP for SCLC-induced MPE was 0.90 (95% CI: 0.78-1.00, P=0.001). At a threshold of 40 pg/mL, proGRP had a sensitivity of 1.00 (95% CI: 0.61-1.00) and specificity of 0.59 (95% CI: 0.52-0.66). The positive likelihood ratio was 2.61 (95% CI: 1.99-3.41), and the negative likelihood ratio was 0. Pleural proGRP has no diagnostic value for MPE, but has high diagnostic accuracy for SCLC-induced MPE. In patients with proGRP levels <40 pg/mL, MPE secondary to SCLC can be excluded.

Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer

Objective To explore the diagnostic value and application effect of the combined detection of CEA (carcinoembryonic antigen), SCC (squamous cell carcinoma antigen), CYFRA21-1 (soluble fragment of cytokeratin 19), NSE (neuron specific enolase) and proGRP (gastrin releasing peptide precursor) in early lung cancer. Method 66 patients who admitted to the hospital from April 2019 to February 2024 were selected as the early stage lung cancer group and the other 159 patients were selected as the benign lung group, in which all subjects were tested for NSE, CEA, ProGRP, CYFRA21-1, and SCC levels and were confirmed by histopathological analysis. In ROC analysis, the cut-off point, AUC, accuracy, sensitivity and specificity between single and combined detection indicators are analyzed. Result The size of cut-off point, AUC, accuracy, sensitivity, specificity, positive and negative detection rate and accuracy rate is 0.3072, 0.790, 89.33%, 0.894, 0.893, 89.40% (59/66), 89.31% (142/159) and 89.33% ((142+59)/225) respectively and it is obviously superior to those of single detection method. Meanwhile, indicator of SCC showed the worst performance by single detection. Conclusion The combined detection indicators have high diagnostic value in early diagnosis of lung cancer, and the sensitivity, positive detection rate, AUC value and accuracy have been significantly improved.

Lack of clinical utility of serum macrophage migration inhibitory factor (MIF) for monitoring therapy response and estimating prognosis in advanced lung cancer.

Lung cancer is a major burden to global health and is still among the most frequent and most lethal malignant diseases. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in a variety of processes including tumorigenesis, formation of a tumor microenvironment and metastasis. It is therefore a potential prognostic biomarker in malignant diseases. In this study, we investigated the applicability of MIF in serum samples as a biomarker in lung cancer. In a retrospective approach, we analyzed the sera of 79 patients with non-small-cell lung cancer (NSCLC) and 14 patients with small-cell lung cancer (SCLC) before the start of chemotherapy, as well as before the second and third chemotherapy cycle, respectively. Serum MIF levels were measured using a sandwich immunoassay with a sulfo-tag-labelled detection antibody, while pro-gastrin releasing peptide (proGRP) levels were determined with an enzyme-linked immunosorbent assay. No difference in serum MIF levels between responders and non-responders to chemotherapy was observed at all time points, while proGRP levels were significantly lower in responders before the second chemotherapy cycle (p = 0.012). No differences in biomarker levels depending on the histopathological classification of NSCLC patients was found. Moreover, in ROC curve analyses MIF was not able to distinguish between responders and non-responders to therapy. proGRP could differentiate between responders and non-responders before the second chemotherapy cycle (p = 0.015) with sensitivities of 43% at 90% and 95% specificity, respectively. Likewise, proGRP yielded significantly longer survival times of patients with low proGRP concentrations before the second chemotherapy cycle (p = 0.015) in Kaplan-Meier analyses, yet MIF showed no significant differences in survival times at all time points. Comparison with the biomarkers CEA and CYFRA 21-1 in the same cohort showed that these established biomarkers clearly performed superior to MIF and proGRP. From the present results, there is no indication that serum MIF may serve as a biomarker in prognosis and monitoring of response to therapy in lung cancer. Limitations of this study include its retrospective design, the inclusion of a larger NSCLC and a smaller SCLC subgroup, the classical chemotherapeutic treatment, the use of a non-diagnostic immunoassay (RUO-test) for MIF measurement and the lack of a validation cohort. Strengths of the study are its highly standardized procedures concerning sample collection, preanalytic treatment, measurements and quality control of the laboratory assays.

Diagnostic value of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in lung adenocarcinoma.

The diagnosis of lung adenocarcinoma (LUAD) leptomeningeal metastasis (LM) remains a clinical challenge. Human epididymis protein 4 (HE4) functions as a novel tumor biomarker for cancers. This study aimed to assess the diagnostic value of cerebrospinal fluid (CSF) HE4, and combined with CEACAM6, for LUAD LM. The CSF HE4 protein level was measured in two independent cohorts by electrochemiluminescence. Test cohort included 58 LUAD LM patients, 22 LUAD patients without LM (Wiot-LM), and 68 normal controls. Validation cohort enrolled 50 LUAD LM patients and 40 normal controls, in parallel with Wiot-LM patients without brain metastases (19 Wiot-LM/BrM patients) or with BrM (26 BrM patients). The CSF level of CEA, CA125, CA153, CA199, CA724, NSE and ProGRP of these samples was measured by electrochemiluminescence, whereas the CSF CEACAM6 level was detected by enzyme-linked immunosorbent assay (ELISA). In addition, the serum level of these biomarkers was detected by same method as CSF. The level of HE4 or CEACAM6 in CSF samples from LUAD LM patients was significantly higher than those from normal controls and Wiot-LM patients. The HE4 or CEACAM6 level in CSF was higher than that in serum of LM patient. The CSF HE4 or CEACAM6 level for distinguished LM from Wiot-LM showed good performance by receiver-operating characteristic analysis. The better discriminative power for LM was achieved when HE4 was combined with CEACAM6. In addition, the CSF HE4 and CEACAM6 level showed little or no difference between Wiot-LM/BrM and BrM patients, the BrM would not significantly influence the HE4 or CEACAM6 level in CSF. The diagnostic power of CSF CA125, CA153, CA199, CA724, NSE and ProGRP for LUAD LM were not ideal. The combination with HE4 and CEACAM6 has the promising application for the diagnosis of LUAD LM.

GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway.

The common characteristics of alcohol-associated liver injury (ALI) include abnormal liver function, infiltration of inflammatory cells, and generation of oxidative stress. The gastrin-releasing peptide receptor (GRPR) is activated by its neuropeptide ligand, gastrin-releasing peptide (GRP). GRP/GRPR appears to induce the production of cytokines in immune cells and promotes neutrophil migration. However, the effects of GRP/GRPR in ALI are unknown. We found high GRPR expression in the liver of patients with alcohol-associated steatohepatitis and increased pro-GRP levels in peripheral blood mononuclear cells of these patients compared with that of the control. Increased expression of GRP may be associated with histone H3 lysine 27 acetylation induced by alcohol, which promotes the expression of GRP and then GRPR binding. Grpr-/- and Grprflox/floxLysMCre mice alleviated ethanol-induced liver injury with relieved steatosis, lower serum alanine aminotransferase, aspartate aminotransferase, triglycerides, malondialdehyde, and superoxide dismutase levels, reduced neutrophil influx, and decreased expression and release of inflammatory cytokines and chemokines. Conversely, the overexpression of GRPR showed opposite effects. The pro-inflammatory and oxidative stress roles of GRPR might be dependent on IRF1-mediated Caspase-1 inflammasome and NOX2-dependent reactive oxygen species pathway, respectively. In addition, we verified the therapeutic and preventive effects of RH-1402, a novel GRPR antagonist, for ALI. A knockout or antagonist of GRPR during excess alcohol intake could have anti-inflammatory and antioxidative roles, as well as provide a platform for histone modification-based therapy for ALI.

Analysis of Diagnostic Value of CTC and CTDNA in Early Lung Cancer.

This paper is the exploration and analysis of the diagnostic value of circulating tumor cells (CTC) and circulating tumor deoxyribonucleic acid (ctDNA) in early non-small cell lung cancer (NSCLC).A total of 125 NSCLC patients that hospitalized from March 2019 to December 2020 were selected, of which 64 subjects with stage I-II were listed as the early-stage group, and 61 patients with stage III-IV were classified as the intermediate-advanced group; In addition, 47 patients with benign pulmonary nodules hospitalized within same period were selected as a group of benign pulmonary nodules, and 50 healthy subjects were enrolled as a control group. The levels of CTC and ctDNA, serum tumor markers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 21-1 (CYFRA21-1) and gastrin-releasing peptide precursor (pro-GRP) were detected. The diagnostic value of CTC and ctDNA in early NSCLC patients was analyzed by ROC curve. The area under the curve of CTC count for early-stage lung cancer was 0. 949 (P=0. 000, 95%CI: 0. 918-0. 980), and ctDNA was 0. 914 (P=0. 000, 95%CI: 0. 866~0. 963). There were significant differences in CTC count and ctDNA among subjects in each group (P<0. 05). CTC count and ctDNA of the early and intermediate-advanced group were remarkably higher than those of the control group and group of benign pulmonary nodules (P<0. 05), and CTC count and ctDNA of patients in the middle-late group were critically higher than those in the early-stage group (P<0. 05). There were significant differences in serum CEA, NSE, CYFRA21-1 and pro-GRP levels among all groups (P<0. 05). The results showed that CTC and ctDNA in NSCLC patients were significantly positively correlated with CEA, NSE, CYFRA21-1 and pro-GRP (P<0. 05). Peripheral blood CTC and ctDNA levels are significantly increased in NSCLC patients. They are positively correlated with serum tumor markers CEA, NSE, CYFRA21-1 and pro-GRP levels, and are related to tumor progression. CTC and ctDNA have high value in the clinical diagnosis of early NSCLC.

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.

Development of exploratory algorithms to aid in risk of malignancy prediction of indeterminate pulmonary nodules

Early detection of lung cancer allows for earlier stage treatment initiation and improved patient prognosis. This report focuses on utilization of combining patient demographic information with non-invasive biomarkers and their potential ability to predict risk of malignancy of nodules. A pilot study cohort of 141 subjects with IPNs (105 stage I cancer and 36 benign nodules) were collected by RUMC. The demographic variables of gender, age, sex, race, ethnicity, nodule size (mm), and smoking pack years, as well as the plasma levels of CA-125, SCC, CEA, HE4, ProGRP, NSE, Cyfra 21-1, hs-CRP, Ferritin, IgG, IgG1, IgG2, IgG3, IgG4, IgE, IgM, IgA, KFLC, and LFLC, were assessed for this cohort. Multivariable analyses of the previously aforementioned biomarkers and demographic variables yielded a reduced algorithm consisting of CA-125, total IgG, IgA, IgM, IgE, LFLC, nodule size, and smoking pack years with improved performance (AUC 0.82, 95 %CI 0.74–0.90) over the same analysis of the demographic variables (age, nodule size, and smoking pack years) alone (AUC 0.70, 95 %CI 0.61–0.78). This reduced algorithm of biomarkers and demographic variables may aid in assessing the risk of IPN malignancy which could be a useful stratification tool in early detection of lung cancer in high-risk subjects.

Effects of Bevacizumab Combined with Chemotherapy on CT, CyFRA21-1, and ProGRP and Prognosis of Lung Cancer Patients under Nursing Intervention.

Objective Molecular targeted drug therapy and chemotherapy are the main treatments for advanced non-small-cell lung cancer, and the combination of both has advantages in prolonging patients' progression-free survival and overall survival. This study investigated the effects of bevacizumab combined with chemotherapy under nursing intervention on CT, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and gastrin-releasing peptide precursor (ProGRP) and prognosis of lung cancer patients. Methods 102 patients with non-small-cell lung cancer admitted to our hospital from January 2018 to May 2019 were divided into observation group and control group, with 51 cases each. The control group was treated with basic chemotherapy, and the observation group was treated with bevacizumab in combination with the control group, and both groups used nursing interventions. The clinical effects, CYFRA21-1 and ProGRP levels, baseline data, CT parameters, 24-month cumulative survival, and the effects of CYFRA21-1 and ProGRP on long-term survival and lung function were compared. Results The disease control rate of the observation group was 94.12%, which was significantly higher than that of the control group (76.47%); after 7 d, 30 d, 60 d, and 90 d of treatment, the levels of CYFRA21-1 and ProGRP were statistically downregulated. The difference in lymph node metastasis, lesion diameter, plain Eff-Z, venous stage, and arterial stage normalized iodine concentrations (NIC) was statistically significant; the survival rate at 24 months in the observation group was 74.51% (38/51); the cumulative survival rate at 24 months in the control group was 52.94% (27/51), and the difference was statistically significant (X2 = 4.980, P = 0.026). The cumulative survival rate at 24 months was significantly lower in patients with high expression of CYFRA21-1 and ProGRP compared with those with low expression of CYFRA21-1 and ProGRP. After treatment, in the observation group, the forceful spirometry (FVC), forceful expiratory volume in one second (FEV1), and FEV1/FVC levels were significantly different from those before treatment and were significantly different from those in the control group. Conclusion Bevacizumab in combination with standard chemotherapy regimens with nursing interventions could benefit patients with advanced non-small-cell lung cancer and had a good prospect of application.

On detection of chromogranin A, synaptophysin, neuronspecific enolase and progastrin-releasing peptide in small cell lung cancer

Lung cancer is one of the most common cancer, there is a significant difference between the treatment and prognosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC tumor cells usually express neuroendocrine tumor (NET) markers, among which there are many studies on chromogranin A (CgA), synaptophysin (Syn), neuronspecific enolase (NSE) and pro-gastrin-releasing peptide (Pro-GRP) with SCLC. The levels of CgA, NSE and pro-GRP were related to the stage of SCLC, which were significantly higher in patients with extensive stage than in patients with limited stage, and their expression was significantly correlated with lower survival rate. Syn as an auxiliary diagnostic index of SCLC is more sensitive than CgA, and has high practical value in the differential diagnosis of SCLC and poorly differentiated squamous cell carcinoma; NSE is the most commonly used tumor marker in SCLC; Pro-GRP has stronger diagnostic advantages than CEA and NSE in distinguishing SCLC from NSCLC. Although these net markers are not specific markers of SCLC, their combined use with each others or combined with CT as an auxiliary diagnostic index may improve the level of differential diagnosis of SCLC, and they have a certain value in the staging of the disease, which is very important for the formulation of SCLC treatment strategy, their detection is conducive to the prevention and control of the disease.

Diagnostic value of HSP90α and related markers in lung cancer.

PurposeTo investigate the expression of heat shock protein 90α (HSP90α) in patients with lung cancer (LC) and the clinical value of HSP90α and other related markers in the diagnosis of LC.MethodsOf 335 patients enrolled in the study cohort, 175 were screened for LC and 160 were healthy (HC). The plasma levels of HSP90α and related markers (CEA, NSE, CYFRA21‐1 and ProGRP) were detected in all individuals in the cohort by enzyme‐linked immunosorbent assay (ELISA). Groups were divided according to gender (male/female), age (≤60 years/>60 years), types of LC (small‐cell carcinoma, squamous carcinoma and adenocarcinoma), staging (I, II, III and IV) and metastasis (metastasis and non‐metastasis) separately. Wilcoxon Mann–Whitney test and Kruskal–Wallis test were used to compare statistical differences between two groups/among the multiple groups for each factor of HSP90α. The r‐value and Kappa were used to compare HSP90α with related markers, and the receiver operating curve (ROC) was used to evaluate the efficacy of plasma HSP90α in predicting LC.ResultsNo statistical difference was found in the plasma level of HSP90α among different age and gender groups (p > 0.05). In the group divided by LC type, staging and metastasis status, there were statistical differences among different groups in HSP90α level (p < 0.05). The levels of HSP90α, CEA, NSE, CYFRA21‐1 and ProGRP in LC groups were significantly higher than HC (p < 0.001). R values of HSP90α correlated with other related markers in the diagnosis of LC (p < 0.05). Although HSP90α and other related markers did not fit the satisfactory conformance, in terms of the positive rate of diagnosis, it was statistically differences in the diagnostic positive rate between HSP90α and each marker (p < 0.01). ROC analysis showed that a plasma HSP90α cut‐off point of 50.02 ng/ml had an optimal predictive value for LC.ConclusionsHSP90α has significant clinical value in early screening and diagnosis of LC. The combined application of HSP90α and related markers can improve the positive rate of early diagnosis of LC effectively.

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.

Predictive value of combined detection tumor markers in the diagnosis of lung cancer

To evaluate the predictive value of combined five tumor markers (TMs) CEA, NSE, SCCA, CYFRA21-1 and ProGRP in the diagnosis of lung cancer(LC). Total of 305 hospitalized patients with LC were enrolled, 100 healthy subjects and 100 patients with benign lung diseases were selected as the healthy control (HC) group and BLD group, respectively. The levels of TMs in serum were detected by Flow fluorescence technique. Positivity rates were analyzed by using Chi-square test,The differences of tumor marker levels were compared using Mann-Whitney test and Kruskal-Wallis test. The Receiver Operating Characteristics (ROC) curve was performed to analyze the diagnosis efficacy of TMs. The combined detection had a higher positive rate in patients with LC, adenoadenocarcinoma, squamous cell carcinoma and SCLC (70.82%, 64.74%, 76.4% and 81.03%, respectively) than each TM considered individually. The serological levels of CEA, NSE, SCCA, CYFRA21-1 in LC group were higher than HC and BLD group. The differences of them among the three groups were statistically significant (χ²=90.599, 32.802, 8.473, 40.397 respectively, all P values were<0.05), ProGRP level had no remarkable difference (χ²=3.366, P>0.05), whereas ProGRP level in SCLC were significantly higher compared with adenocarcinoma (Z=6.404,P<0.001) and squamous cell carcinoma (Z=5.765,P<0.001) group. The combined detection difference of positive rate between the early stages(stageⅠ and stage Ⅱ)and the advanced stages (stage Ⅲ and stage Ⅳ) were statistically significant(χ²=24.941, P<0.001).The positive rate of combined detection in the diagnosis of lung cancer lymph node metastasis(76.31%) or distant metastasis(78.18%) was significantly higher than that of single detection. Meanwhile, the positive rate of combined detection in patients with lymph node metastasis or distant metastasis was significantly higher than that in patients without metastasis(χ²=24.60, 9.50 respectively, all P values were<0.05).The combined detection had a better sensitivity(70.82%), accuracy(69.10%)and negative predictive value (59.91%)in LC group than each TM considered individually.The ROC curve showed that the AUC of combined detection in the diagnosis of LC, lung adenocarcinoma, lung squamous cell carcinoma and SCLC were 0.769, 0.780, 0.766 and 0.831, respectively.The combined detection of five tumor markers of CEA, NSE, SCCA, CYFRA21-1 and ProGRP by flow fluorescence technique can improve the diagnostic efficiency of lung cancer.

The value of combined detection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the differential diagnosis of lung cancer.

BackgroundTo investigate the value of carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag), and gastrin-releasing peptide (pro-GRP) in the differential diagnosis of lung cancer.MethodsWe enrolled 120 patients with malignant lung cancer who were treated at our hospital between June 2018 to June 2020. A further 58 patients with benign lung tumors and 60 healthy volunteers were also enrolled. Serum levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP were determined and compared across different populations, different pathological types, and different TNM stages. An ROC curve was drawn to evaluate the value of the four indicators when combined for the diagnosis of lung cancer.ResultsThe levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the malignant group were significantly higher than those in the benign and healthy groups (P<0.05). CEA in adenocarcinoma was significantly higher than that in squamous cell carcinoma (SCC) and small cell carcinoma (P>0.05), and CYFRA21-1 in non-small cell carcinoma was significantly higher than that in small cell carcinoma (P<0.05). Pro-GRP in small cell carcinoma was significantly higher than that in non-small cell carcinoma (P<0.05), and the SCC-Ag level in SCC was significantly higher than that in small cell carcinoma and adenocarcinoma (P<0.05). There was no statistically significant difference in CEA among various pathological types (P>0.05). However, there were significant differences in the levels of CEA and pro-GRP in different TMN stages (P<0.05), and in the levels of CEA and pro-GRP in different TMN stages (P<0.05) where from stage I to stage IV CEA, pro -GRP levels increased. There was a significant difference in CYFRA21-1 levels in stages I–III (P<0.05), and in stages III and IV, although there was no statistically significant difference in SCC-Ag in different stages (P>0.05). The area under the curve (AUC) for the combined diagnosis of lung cancer with the four markers was 0.9250 (95% CI: 0.8866-0.9634), the sensitivity was 93.29%, and the specificity was 84.32%.ConclusionsJoint inspection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP levels has certain clinical value for the differential diagnosis of lung cancer.

Elevated basal serum levels of calcitonin and simultaneous surgery of MEN2A-specific tumors.

Multiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome caused almost by germline RET mutation, and characterized by medullary thyroid carcinoma (MTC), in combination or not with pheochromocytoma (PHEO), hyperparathyroidism (HPTH), cutaneous lichen amyloidosis (CLA), and Hirschsprung's disease (HD). The basal serum calcitonin (Ctn)/carcinoembryonic antigen (CEA) levels are significantly correlated with the MTC stage. Metachronous surgery of MEN2A-specific tumors is a routine procedure. We aimed to explore the clinical significance of pro-gastrin-releasing peptide (proGRP) in MTC with elevated Ctn and simultaneous surgery of MEN2A-specific tumors. We retrospectively investigated 8 RET mutation carriers of 2 Chinese pedigrees with MEN2A. Clinical profiles, imaging examinations, preoperative and postoperative biochemical data, surgical procedures, and follow-up records were evaluated. Three patients showed levels of elevated Ctn but normal proGRP. Among them, one patient (FAIII-6) in Family A (one for RET C634R mutation), diagnosed with bilateral MTC, left PHEO, bilateral HPTH, and CLA, classified as MEN2A-related CLA subtype, underwent successfully simultaneous adrenal-sparing surgery (ASS), total thyroidectomy (TT), and parathyroidectomy, while TT of the other two patients (FBII-3 and FBIII-7) diagnosed with bilateral MTC in Family B (all for RET C618R mutation) were performed. Unexpectedly, the absence of neck lymph node MTC metastasis was indicated by histopathological examination. Postoperatively, all had consistently "undetectable" or normal levels of Ctn/CEA during follow-up. Patients with normal proGRP, despite high levels of Ctn, might have no regional lymph node MTC metastasis, and neck dissection should be avoided. Moreover, simultaneous surgery for coexistent PHEO and either MTC or HPTH is an approach of choice to use as an alternative treatment pattern. Recognition of MEN2A-related CLA and subsequently early screening of RET mutation may be favorable for timely management of MEN2A-specific tumors.