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cN-II expression predicts survival in patients receiving gemcitabine for advanced non-small cell lung cancer

Pascal Sève1, John R Mackey, Sylvie Isaac

  • 1Service de Médecine Interne, Hôtel Dieu, 1 place de l'Hôpital, 69288 Lyon Cedex 02, France.

Lung Cancer (Amsterdam, Netherlands)
|June 1, 2005
PubMed

Insights

High expression of carboxylesterase II (cN-II) predicts better overall survival in non-small cell lung cancer (NSCLC) patients treated with gemcitabine chemotherapy. Low cN-II levels indicate a poorer prognosis, highlighting its role in treatment outcomes.

Area of Science:

  • Oncology
  • Pharmacogenomics
  • Cancer Biomarkers

Background:

  • Gemcitabine resistance in non-small cell lung cancer (NSCLC) is multifactorial, involving drug penetration, metabolism, and targeting.
  • Previous studies indicate that human equilibrative nucleoside transporter 1 (hENT1)-deficient cells exhibit gemcitabine resistance.
  • Overexpression of nucleotidases, such as carboxylesterase II (cN-II), is frequently observed in gemcitabine-resistant models.

Purpose of the Study:

  • To investigate the association between the protein abundance of cN-II, hENT1, human concentrative nucleoside transporter 3 (hCNT3), and deoxycytidine kinase (dCK) and gemcitabine chemotherapy outcomes in NSCLC patients.
  • To identify potential predictive biomarkers for response to gemcitabine-based chemotherapy in treatment-naïve advanced or metastatic NSCLC.

Main Methods:

  • Immunohistochemical analysis was performed on malignant cells from 43 treatment-naïve NSCLC patients.
  • Protein expression levels of cN-II, hENT1, hCNT3, and dCK were assessed.
  • Chemotherapy response, progression-free survival (PFS), and overall survival (OS) were correlated with protein abundance.

Main Results:

  • Only 16% of samples expressed detectable hENT1, while 42% expressed hCNT3, 86% expressed cN-II, and 66% expressed dCK.
  • Univariate analysis revealed that only cN-II expression levels correlated with overall survival (OS).
  • Patients with low cN-II expression (<40% positive cells) had significantly worse OS (6 months) compared to those with high expression (11 months).

Conclusions:

  • Carboxylesterase II (cN-II) protein expression levels can identify subgroups of NSCLC patients with different outcomes under gemcitabine-based therapy.
  • cN-II emerged as the sole predictive factor for overall survival in multivariate analysis, independent of age, sex, weight loss, and stage.
  • Larger prospective studies are recommended to confirm the predictive value of cN-II in NSCLC patients receiving gemcitabine chemotherapy.

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