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Enriched sera protein profiling for detection of non-small cell lung cancer biomarkers.

ABSTRACT: BACKGROUND: Non Small Cell Lung Cancer (NSCLC) is the major cause of cancer related-death. Many patients receive diagnosis at advanced stage leading to a poor prognosis. At present, no satisfactory screening tests are available in clinical practice and the discovery and validation of new biomarkers is mandatory. Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-ToF-MS) is a recent high-throughput technique used to detect new tumour markers. In this study we performed SELDI-ToF-MS analysis on serum samples treated with the ProteoMiner™ kit, a combinatorial library of hexapeptide ligands coupled to beads, to reduce the wide dynamic range of protein concentration in the sample. Serum from 44 NSCLC patients and 19 healthy controls were analyzed with IMAC30-Cu and H50 ProteinChip Arrays. RESULTS: Comparing SELDI-ToF-MS protein profiles of NSCLC patients and healthy controls, 28 protein peaks were found significantly different (p < 0.05), and were used as predictors to build decision classification trees. This statistical analysis selected 10 protein peaks in the low-mass range (2-24 kDa) and 6 in the high-mass range (40-80 kDa). The classification models for the low-mass range had a sensitivity and specificity of 70.45% (31/44) and 68.42% (13/19) for IMAC30-Cu, and 72.73% (32/44) and 73.68% (14/19) for H50 ProteinChip Arrays. CONCLUSIONS: These preliminary results suggest that SELDI-ToF-MS protein profiling of serum samples pretreated with ProteoMiner™ can improve the discovery of protein peaks differentially expressed between NSCLC patients and healthy subjects, useful to build classification algorithms with high sensitivity and specificity. However, identification of the significantly different protein peaks needs further study in order to provide a better understanding of the biological nature of these potential biomarkers and their role in the underlying disease process.

SUBMITTER: Monari E

PROVIDER: S-EPMC3184051 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Enriched sera protein profiling for detection of non-small cell lung cancer biomarkers.

Monari Emanuela E Casali Christian C Cuoghi Aurora A Nesci Jessica J Bellei Elisa E Bergamini Stefania S Fantoni Luca I LI Natali Pamela P Morandi Uliano U Tomasi Aldo A

Proteome science 20110919 1

<h4>Background</h4>Non Small Cell Lung Cancer (NSCLC) is the major cause of cancer related-death. Many patients receive diagnosis at advanced stage leading to a poor prognosis. At present, no satisfactory screening tests are available in clinical practice and the discovery and validation of new biomarkers is mandatory. Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-ToF-MS) is a recent high-throughput technique used to detect new tumour markers. In this study ...[more]

PMID: 21929752

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Project description:ObjectiveSince the inefficient cancer management is caused by inaccurate diagnoses, there is a need for minimally invasive method to improve the diagnostic accuracy of non-small-cell lung (NSCLC). This study intended to detect miR-340 and miR-450b-5p levels in plasma from NSCLC patients and to assess the potential values for the prediction of tumor development and prognosis.MethodsA GSE64591 dataset included 200 samples (100 early-stage NSCLC patients and 100 noncancer control) aimed to identify a panel of circulating miRNAs in plasma. The levels of miR-340 and miR-450b-5p in plasma from NSCLC patients (n = 120) and healthy controls (n = 120) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of plasma miR-340 and miR-450b-5p were performed using receiver operating curves (ROC), Kaplan-Meier method, and Cox regression analysis.ResultsmiR-450b-5p and miR-340 in plasma was significant difference between early-stage NSCLC patients and noncancer control by searching the GSE64591 dataset. When compared with the healthy controls, the plasma miR-340 was decreased in the NSCLC patients, but the plasma miR-450b-5p was increased. NSCLC patients could be distinguished accurately from healthy controls by the circulating miR-340 and miR-450b-5p with the AUC of 0.740 (95% CI: 0.677~0.804) and of 0.808 (95% CI: 0.754~0.861), respectively. With these two markers, the specificity and sensitivity were 78.33% and 77.5% with the AUC of 0.862. Patients with advanced T, N, and TNM stage demonstrated lower plasma miR-340 and higher plasma miR-450b-5p, and both of them were correlated with the prognosis of NSCLC patients. Furthermore, plasma miR-340 was also negatively correlated with tumor grade. All clinicopathological variables significantly associated to prognosis were T stage, N stage, TNM stage, tumor grade, and plasma levels of miR-340 and miR-450b-5p in univariate Cox regression analysis. The variables that retained their significance in the multivariate model were T stage, plasma miR-340, and plasma miR-450b-5p.ConclusionThe plasma levels of miR-340 combined with miR-450b-5p potentially define core biomarker signatures for improving the accuracy of NSCLC diagnosis. Moreover, circulating miR-340 and miR-450b-5p are independent biomarkers of survival in nonmetastatic NSCLC patients.

Dataset Information

Enriched sera protein profiling for detection of non-small cell lung cancer biomarkers.

Publications

Enriched sera protein profiling for detection of non-small cell lung cancer biomarkers.

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