Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis.

BACKGROUND: Immunoregulatory cytokines may play a fundamental role in tumor growth and metastases. Their effects are mediated through complex regulatory networks. Human cytokine profiles could define patient subgroups and represent new potential biomarkers. The aim of this study was to associate a cytokine profile obtained through data mining with the clinical characteristics of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We conducted a prospective study of the plasma levels of 14 immunoregulatory cytokines by ELISA and a cytometric bead array assay in 110 NSCLC patients before chemotherapy and 25 control subjects. Cytokine levels and data-mining profiles were associated with clinical, quality of life and pathological outcomes. RESULTS: NSCLC patients had higher levels of interleukin (IL)-6, IL-8, IL-12p70, IL-17a and interferon (IFN)-γ, and lower levels of IL-33 and IL-29 compared with controls. The pro-inflammatory cytokines IL-1b, IL-6 and IL-8 were associated with lower hemoglobin levels, worse functional performance status (Eastern Cooperative Oncology Group, ECOG), fatigue and hyporexia. The anti-inflammatory cytokines IL-4, IL-10 and IL-33 were associated with anorexia and lower body mass index. We identified three clusters of patients according to data-mining analysis with different overall survival (OS; 25.4, 16.8 and 5.09 months, respectively, P = 0.0012). Multivariate analysis showed that ECOG performance status and data-mining clusters were significantly associated with OS (RR 3.59, [95% CI 1.9-6.7], P < 0.001 and 2.2, [1.2-3.8], P = 0.005). CONCLUSION: Our results provide evidence that complex cytokine networks may be used to identify patient subgroups with different prognoses in advanced NSCLC. These cytokines may represent potential biomarkers, particularly in the immunotherapy era in cancer research.

Diagnostic methods of primary tuberculous pleural effusion in a region with high prevalence of tuberculosis. A study in Mexican population.

STUDY OBJECTIVES: 1) To determine the age distribution of the patients with pleural tuberculosis in a region with high prevalence of tuberculosis; and 2) to evaluate the efficiency of the methods used in its diagnosis. SETTING: The National Institute of Respiratory Diseases in Mexico City, a tertiary reference center for pulmonary diseases. DESIGN: A retrospective study. PATIENTS: 452 consecutive inpatients with diagnosis of pleural effusion from January 1991 to September 1996 were reviewed: 133 patients had a diagnosis of tuberculous pleural effusion of primary origin without parenchymal abnormalities by chest roetgenogram. The others were excluded because of reactivated tuberculosis or non-tuberculous effusion. MEASUREMENTS AND RESULTS: The patients had a mean age of 42 +/- 17 years (98 male, 35 female). Pleural granulomas in the morphological study were found in 87% whereas the baciloscopy and the culture of the fluid were positive in only 8% and 19% respectively. The determination of adenosine deaminase (ADA) gave a diagnostic yield of 84%. CONCLUSIONS: 1) Primary tuberculosis pleural effusion, reported in the English literature, was also present in our adults; 2) the pleural biopsy continued to be the most effective method in the diagnosis of the pathology; and 3) the determination of ADA in an area with high prevalence of the disease was a reliable and unexpensive diagnostic method.

PIP: It is often difficult to diagnose tuberculosis (TB) pleural effusion because the search for Mycobacterium tuberculosis in fluid, or the identification of historical alterations in the pleural biopsy are often false negative. The diagnosis, however, must be timely since 43-65% of patients may develop an active pulmonary TB in the next 3-5 years. To determine the age distribution of patients with pleural TB, the authors reviewed the charts of 452 consecutive inpatients from January 1991 to September 1996 hospitalized at Mexico's National Institute of Respiratory Diseases with a diagnosis of the condition. 133 patients were diagnosed with TB pleural effusion of primary origin without parenchymal abnormalities according to chest roentgenogram. These 98 men and 35 women were of mean age 42 years. Pleural granulomas were identified in 87% of subjects while fluid baciloscopy and culture were positive in only 8% and 19%, respectively. The determination of adenosine deaminase (ADA) produced a diagnostic yield of 84%. Based upon their findings, the authors stress that primary TB pleural effusion may also be seen in adults, closed pleural biopsy remains the most effective diagnostic method, and ADA level is a cheap diagnostic method in countries with a high prevalence of TB.