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

Abstract

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.
 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.
 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<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<0.001). Serial measurements of proGRP in SCLC patients showed a decrease in responsive chemotherapy patients.

Pro-Gastrin-Releasing Peptide as a Biomarker in Lung Neuroendocrine Neoplasm

“…An Italian study from 2021 [ 36 ] obtained similar results: higher levels of ProGRP were found in patients with SCLC (1484 pg/mL) compared to healthy subjects (36.1 pg/mL) and patients with non-SCLC (45 pg/mL).…”

Improvement of differential diagnosis of lung cancer by use of multiple protein tumor marker combinations

“…Furthermore, especially ProGRP and NSE showed a good discriminative ability between NSCLC and SCLC, in accordance with our results. Barchiesi et al [26] conducted a small prospective investigation which validated the distinguishing capacity of NSE and, particularly, ProGRP (with a sensitivity of 82.4% and a specificity of 93.3%). This capability was further improved when both were used in combination (86.7% sensitivity at 96.6% specificity).…”

Clinical Efficacy of Anti-programmed Death Ligand 1 Immunotherapy Combined with Chemoradiotherapy in the Treatment of Limited-stage Small Cell Lung Cancer and Its Effect on Serum Tumor Markers and T Lymphocyte Subsets

“…Tumor markers are produced and secreted by human tumor tissues and cells [18] , and their levels are positively correlated with the severity of the patient's condition [19] NSE is a sensitive marker of neuroendocrine tumors, which can re ect the occurrence and progress of tumors; Pro GRP is an important marker for tumor condition and prognosis evaluation. Its expression level is positively correlated with the severity of the disease, which is of great signi cance for disease condition evaluation and prognosis prediction [20][21][22] . CYFRA21-1 can be released into the blood when tumor cells are lysed or necrotic, which has a high diagnostic and e cacy assessment in SCLC patients [23] .There was no signi cant difference between the two groups of patients before and after CEA treatment, which may be related to the fact that CEA positive rates are more frequently expressed in lung adenocarcinoma [24] .There was no signi cant difference in baseline markers between the two groups in this research.…”