New and old biomarkers in the differential diagnosis of lung cancer: Pro-gastrin-releasing peptide in comparison with neuron-specific enolase, carcinoembryonic antigen, and CYFRA 21-1

Mauro, Cristian; Passerini, Rita; Spaggiari, Lorenzo; Galetta, Domenico; Radice, Davide; Lentati, Paola; Sandri, Maria-Teresa

doi:10.1177/1724600819834235

Cited by 19 publications

(13 citation statements)

References 30 publications

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“…When looking at the diagnostic performance of 6 biomarkers individually on histologic types, NSE, HE4, and ProGRP showed relative high AUC sensitivity and speci city, with ProGRP presenting the highest speci city for SCLC. These results are similar with other reports on ProGRP [26][27][28].…”

Section: Diagnostic Performance Of 6 Biomarkers On Histological Typessupporting

confidence: 93%

Histological specificity and diagnostic performance of a six-biomarker panel of lung cancer: An evaluation of a geographically-based multicenter study in China

Li¹,

Zhang²,

Jiang³

et al. 2021

Preprint

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Background: Lung cancer is the most common neoplasm among all cancers worldwide. Early diagnosis with minimal invasive procedures is ideal for lowering the patients’ burden and increasing survival rates. The value of serum tumor biomarkers used in lung cancer screening is still controversial in clinical practice.Methods: Serum levels of ProGRP, NSE, SCC-Ag, CEA, CYFRA21-1, and HE4 were measured using the chemiluminescence immunoassay in apparently healthy Chinese individuals, as well as in those with benign non-cancerous diseases, lung cancer patients, and those suffering other types of malignancies. Data was analyzed utilizing the SPSS version 18.0 statistical software. Results: All 6 serum biomarkers in lung cancers were significantly higher than in benign non-cancerous diseases and healthy controls. HE4 levels in benign diseases were significantly higher than in healthy controls. SCC-Ag, CEA, and CYFRA21-1 levels in lung cancers were significantly higher than in other malignancies. ProGRP and NSE levels in SCLC were significantly higher than in other histologic types; SCC-Ag and CYFRA21-1 levels in SCC were significantly higher than in other histologic types; the HE4 level in SCLC was also significantly higher than in SCC and adenocarcinoma, while adenocarcinoma had the highest serum CEA level comparing to SCC and SCLC. Serum ProGRP, NSE, and HE4 in SCLC were significantly higher than in NSCLC, SCC-Ag level in NSCLC was significantly higher than in SCLC. All biomarkers in advanced stages were significantly higher than in lower stages. NSE, HE4, and ProGRP presented relative high performance in SCLC. CYFRA21-1, HE4, and SCC-Ag indicated relative high performance in SCC. All biomarkers had relatively low performance on adenocarcinoma histologic type. The best performance of 2-marker combination was SCC-Ag+CYFRA21-1 for SCC, ProGRP+NSE for SCLC, CEA+CYFRA21-1 for adenocarcinoma. A combination of SCC+CEA+CYFRA21-1 gained highest performance for NSCLC.Conclusions: A 6-biomarker panel had capability on characterizing lung cancer and presented high performance individually and combinatorically on different histologic types of the neoplasm. HE4 showed high sensitivity to all histologic types of the malignancy; however, one should be cautious since its level also increased in benign non-cancerous diseases.

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Section: Diagnostic Performance Of 6 Biomarkers On Histological Typessupporting

confidence: 93%

Histological specificity and diagnostic performance of a six-biomarker panel of lung cancer: An evaluation of a geographically-based multicenter study in China

Li¹,

Zhang²,

Jiang³

et al. 2021

Preprint

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“…However, our results with more combined TMs did not display better diagnostic efficacy, and the feasibility of this diagnostic panel required further assessment of cost-effectiveness analysis. Mauro et al 16 ran a multivariable logistic regression analysis to quantify the added value of ProGRP to other conventional markers including ProGRP, NSE, CEA, and CYFRA 21-1, but no markers improved the performance of ProGRP in the diagnosis of SCLC with respect to benign lung disease. In our study, the logistic regression predictive model including SCC, NSE, and ProGRP obtained a preferable efficacy (AUC: 0.888; 95% CI: 0.846–0.929; sensitivity: 71.3%; specificity: 95.0%).…”

Section: Discussionmentioning

confidence: 99%

“…14, 15 The diagnostic performance of ProGRP and NSE individually seemed better than other conventional tumor markers for SCLC; however, there are still some deficiencies. 16–18 Some researchers attempted to improve their diagnostic efficacy in combination with other tumor markers including CEA, TPA, TPS, SCC, CA125, CA19-9, HE4, and CYFRA 21-1, etc. 9, 19–25 However, no consensus has been reached with respect to tumor markers’ combined pattern in SCLC diagnosis.…”

Section: Introductionmentioning

confidence: 99%

The diagnostic value of the combination of carcinoembryonic antigen, squamous cell carcinoma-related antigen, CYFRA 21-1, neuron-specific enolase, tissue polypeptide antigen, and progastrin-releasing peptide in small cell lung cancer discrimination

et al. 2021

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Background The diagnostic value of six tumor markers was investigated and the appropriate combinations of those tumor markers to discriminate small cell lung cancer was explored. Methods Patients suspected with lung cancer (1938) were retrospectively analyzed. Candidate tumor markers from carcinoembryonic antigen (CEA), squamous cell carcinoma-related antigen (SCC), cytokeratin 19 fragment 21-1 (CYFRA 21-1), neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), and progastrin releasing peptide (ProGRP) were selected to construct a logistic regression model. The receiver operating characteristic curve was used for evaluating the diagnostic value of the tumor markers and the predictive model. Results ProGRP had the highest positive rate (72.3%) in diagnosed small cell lung cancer, followed by neuron-specific enolase (68.3%), CYFRA21-1 (50.5%), carcinoembryonic antigen (45.5%), tissue polypeptide antigen (30.7%), and squamous cell carcinoma-related antigen (5.9%). The predictive model for small cell lung cancer discrimination was established, which yielded the highest area under the curve (0.888; 95% confidence interval: 0.846–0.929), with a sensitivity of 71.3%, a specificity of 95.0%, a positive predictive value of 49.0%, and a negative predictive value of 98.0%. Conclusions Combining tumor markers can improve the efficacy for small cell lung cancer discrimination. A predictive model has been established in small cell lung cancer differential diagnosis with preferable efficacy.

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“…Serum tumor markers remain a simple and economical tool for diagnosing and predicting the prognosis of lung cancer patients. Many serum components such as CEA, CYFRA 21-1, SCC, and NSE have been investigated and considered to be markers of this malignancy (Mauro et al 2019). With respect to the relationship of serum tumor markers and BM, previous studies have demonstrated that patients with high CEA level had a higher risk of BM and poor prognosis (Lee et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Huang

Weng

et al. 2019

J Cancer Res Clin Oncol

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Purpose The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a vital role in cancer development and progression. This study aimed to investigate the relationship between genotype variants in mTORC1 pathway and the risk of brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC). Methods We extracted genomic DNA from blood samples of 501 NSCLC patients and genotyped eight single-nucleotide polymorphisms (SNPs) in three core genes [mammalian target of rapamycin (mTOR), mammalian lethal with sec-13 protein 8 (mLST8) and regulatory-associated protein of mTOR (RPTOR)] of the mTORC1 pathway. The associations between these SNPs and the risk of BM development were assessed. Results The AG/GG genotype of mLST8:rs26865 and TC/CC genotype of mLST8:rs3160 were associated with an increased risk of BM [hazard ratios (HR) 2.938, 95% confidence interval (CI) 1.664-5.189, p < 0.001 and HR = 2.490, 95% CI = 1.543-4.016, p < 0.001, respectively]. These risk polymorphisms had a cumulative effect on BM risk, with two risk genotypes exhibiting the highest increased risk (p < 0.001). Furthermore, these risk SNPs were associated with the lymph node metastasis (N2/3), body mass index (BMI) (≥ 25 kg/m 2), high level of squamous cell carcinoma (SCC) antigen and Ki-67 proliferation index. Moreover, patients with AG/GG genotype of mLST8:rs26865 had significantly lower median overall survival than those with AA genotype (12.1 months versus 21.6 months, p = 0.04). Conclusions Our results indicate that polymorphisms in mTORC1 pathway were significantly associated with increased risk of BM and may be valuable biomarkers to identify NSCLC patients with a high risk of BM. Keywords mTORC1 • Genetic polymorphisms • Brain metastasis • Risk • Biomarker Yiquan Xu and Yina Huang have contributed equally to the article and share the first authorship.

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New and old biomarkers in the differential diagnosis of lung cancer: Pro-gastrin-releasing peptide in comparison with neuron-specific enolase, carcinoembryonic antigen, and CYFRA 21-1

Cited by 19 publications

References 30 publications

Histological specificity and diagnostic performance of a six-biomarker panel of lung cancer: An evaluation of a geographically-based multicenter study in China

Histological specificity and diagnostic performance of a six-biomarker panel of lung cancer: An evaluation of a geographically-based multicenter study in China

The diagnostic value of the combination of carcinoembryonic antigen, squamous cell carcinoma-related antigen, CYFRA 21-1, neuron-specific enolase, tissue polypeptide antigen, and progastrin-releasing peptide in small cell lung cancer discrimination

Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

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