Serum Cripto-1 is a novel biomarker for non-small cell lung cancer diagnosis and prognosis

Clin Respir J. 2017 Nov;11(6):765-771. doi: 10.1111/crj.12414. Epub 2016 Jan 25.

Abstract

Introduction: Cripto-1 (CR-1) is highly expressed in several different types of human tumors. However, the clinical significance of CR-1 expression in serum specimens from non-small cell lung cancer (NSCLC) patients has not yet been determined.

Objectives: The aim of this study was to explore the diagnostic and prognostic value of serum CR-1 levels in patients with NSCLC.

Methods: Serum specimens from 592 NSCLC patients, 180 benign lung disease patients and 240 healthy controls were collected. The concentrations of CR-1 were measured by sandwich enzyme-linked immunosorbent assay.

Results: Patients with NSCLC had higher serum CR-1 levels than the controls (P < 0.01) and patients with benign lung diseases (P < 0.01). When a cutoff point of 1.8 ng/mL was selected (diagnostic specificity 95%), the diagnostic sensitivity for NSCLC is 56.8%. About 37.5% of carcinoembryonic antigen (CEA)-negative lung cancer patients were CR-1 positive at 95% specificity. In patients with stage I/II lung cancer, use of these two markers in combination results in almost 21% increase in sensitivity, at 95% specificity, compared with CEA alone. Uni-variate analysis revealed that NSCLC patients with positive CR-1 had a shorter overall survival (OS) and progression-free survival (PFS) than those with negative CR-1 [hazard ratio (HR) of 2.93, P = 0.005; HR of 2.12, P = 0.005]. Cox multi-variate analysis indicated that CR-1 was an independent prognostic indicator of PFS and OS (HR of 1.91, P = 0.006; HR of 1.82, P = 0.007). Kaplan-Meier survival curves further confirmed that patients with negative CR-1 had longer PFS and OS (P = 0.026 and P = 0.011, respectively).

Conclusions: In conclusion, measurement of serum CR-1 is a useful diagnostic and prognostic marker for NSCLC patients.

Keywords: Cripto-1; biomarker; diagnosis; non-small cell lung cancer; prognosis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Carcinoembryonic Antigen / blood
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • GPI-Linked Proteins / blood*
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Lung / pathology
  • Lung Neoplasms / blood*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • TDGF1 protein, human