Irena Porębska

Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol.

Serum and whole blood Zn, Cu and Mn profiles and their relation to redox status in lung cancer patients

Disturbed redox status may be critical to lung cancerogenesis, however little research has been conducted on general changes in total redox status in lung cancer. Levels and activities of antioxidants, especially enzymatic ones, are related to trace element concentration. Trace element status is often disturbed in cancers, however no studies concerning the association between redox and trace element status have been performed for lung cancer. We hypothesized that disturbed redox status in lung cancer patients is partially determined by trace elements while their distribution amongst blood compartments may differ compared to healthy subjects. Blood samples from lung cancer patients (n=44) and control subjects (n=44) were collected to assess redox and trace element status. Serum and whole blood Cu and Mn levels were determined with GF-AAS, and Zn-with F-AAS. In serum the total antioxidant status (TAS) was determined with the commercial kit TAS (Randox, UK), total oxidant status (TOS) was determined based on the method developed by Erel and the oxidative stress index (OSI) was calculated. Total protein (T-Prot), albumin (Alb), uric acid (UA) and total bilirubin (T-Bil) concentrations were measured with an auto-analyser (Konelab 20i, Thermoscientific, USA), SOD and CAT activity - with commercially available kits (Cayman, USA). The level of TAS, T-Prot, Alb, T-Bil, the activity of SOD, the concentration of whole blood Mn as well as serum and whole blood Zn were lower while TOS, OSI, serum Cu levels and serum Cu:Zn ratios were higher in lung cancer patients compared to the control group. In the lung cancer group TAS correlated positively with Alb and UA, serum Zn and negatively with whole blood Mn. Additionally, SOD positively correlated with the whole blood Mn and Cu:Zn ratio, while CAT - negatively with the whole blood Cu:Zn ratio. In the lung cancer sub-group at clinical stage I-II, TOS additionally negatively correlated with whole blood Zn, and CAT negatively with serum Cu and Cu:Zn ratio. In advanced lung cancer, we found a positive correlation between TAS and serum Zn, and a negative one - with serum Cu:Zn ratio. We observed a similar correlation between endogenous non-enzymatic antioxidants and TAS in the control group, however considerably fewer correlations between trace elements and antioxidants were observed. This study supports the hypothesis that disturbed redox status in lung cancer patients is linked with alterations in trace element status regarding Zn, Mn and Cu. Moreover, the type of biological fluid influences both - alterations in the metal profile and relationships with redox status parameters.

Lung cancer in patients under the age of 40 years

Aim of the study In the paper clinical cases of individuals diagnosed with lung cancer below the age of 40 years have been analyzed. Material and methods The analysis included: sex, age, clinical symptoms found before and at the moment of diagnosis, character of changes visible in radiological imaging, time that passed from the first symptoms to reporting to a doctor and to establishing a diagnosis, type of diagnostic method used in establishing the final diagnosis, histopathologic type of cancer, degree of cancer progression. Results The results have been compared with a peer group who had been diagnosed 20 years earlier. Currently 7% of patients were diagnosed at the age of 25 or younger, whereas in the previous cohort patients in this age constituted 2%. The predominant pathological type was adenocarcinoma (currently 33%, previously 4%) in contrast to the earlier group in which 57% of patients had small cell lung cancer (57%). The incidence is equally distributed between both sexes, although there is an evident increase in female lung cancer cases. In the majority of patients the clinical presentation is a peripheral mass on chest X-ray. 20% of patients present pleural effusion on diagnosis. Patients reported the following complaints: breathlessness, chest pain, weight loss and fatigue. The majority of cases were diagnosed in advanced stages on the basis of a bronchoscopy acquired specimen. Time course from symptoms to diagnosis tends to be shorter than 20 years ago.

Identification of Soluble Supramolecular FN-fibrin Complexes in Human Plasma

SDS-agarose FN immunoblotting of 257 normal and pathological human plasma samples revealed the ladder pattern of multiple plasma FN bands which corresponded to FN monomer and dimer, and 5 FN-fibrin bands with increasing molecular masses. The FN-fibrin bands of about 750 kDa, 1000 kDa, 1300 kDa, 1600 kDa, and 1900 kDa appeared more frequently and in significantly higher relative amounts in the pathological samples (P < 0.000) than in relatively healthy individuals. The revealing of high-molecular FN-fibrin complexes by SDS-agarose FN immunobloting might have the potential to become a laboratory biomarker of some diseases in which the coagulation system is triggered.

The influence of hypertension on daytime sleepiness in obstructive sleep apnea

Daytime sleepiness is a common symptom among hypertensive patients. The aim of this study was to determine subjective sleepiness assessed by Epworth Sleepiness Scale (ESS) and to asses sleep architecture in 304 patients with arterial hypertension. All patients underwent a standardized diagnostic overnight, polysomnography. The control group consisted of 67 normotensives. The hypertensive patients had a decreased sleep efficiency, mean and minimum oxygen saturation levels, and increased apnea/hypopnea index and oxygen desaturation index compared with normotensive patients. The lower ratio of N3 sleep, higher of N2 sleep, and decreased sleep efficiency was observed in hypertensives without obstructive sleep apnea (OSA). In the moderate to severe OSA groups, the total ESS score was significantly lower in hypertensives compared with normotensives. The ESS scores decreased with age in hypertensives, but not in normotensives. The study showed that ESS total score is lower in hypertensives than in normotensives with OSA, making the OSA more difficult to suspect. Thus, the low ESS score in hypertensives should not discourage further evaluation.

Total antioxidant status in lung cancer is associated with levels of endogenous antioxidants and disease stage rather than lifestyle factors – preliminary study

Aim of the study Decreased total antioxidant capacity (TAC) has been reported in different neoplasms, including lung cancer. However, no study concerning the relationship between endogenous antioxidants, lifestyle factors, and TAC has been conducted among lung cancer patients. The purpose of the study was to investigate the associations between endogenous antioxidants, severity of disease, lifestyle factors, and TAC in lung cancer patients. Material and methods The study was conducted among 59 lung cancer patients. The levels of total antioxidant status (ATBS method), endogenous antioxidants, and C-reactive protein were measured in patients’ sera automatically. Dietary habits of the subjects were evaluated based on the Food Frequency Questionnaire (FFQ) on the day of admission to hospital. Results We found a positive correlation between serum albumin, uric acid (UA), and TAC and a negative correlation between CRP and TAC. Moreover, TAC was significantly positively associated with disease stage. We did not find any significant relationship between the frequency of selected food consumption and TAC in lung cancer patients, except for a positive correlation between the frequency of refined cereal products consumption and TAC level. Smoking status did not correlate with TAC. Conclusions Total antioxidant status of lung cancer patients results from their disease stage and levels of endogenous antioxidants rather than from lifestyle factors. The lack of influence of diet and smoking on the TAC presumably result from disturbed homeostasis in which cancer, while developing, could determine the redox state to a greater extent than lifestyle factors.

Dietary habits of lung cancer patients from the Lower Silesia region of Poland

Aim of the study Assessment of lung cancer patients’ dietary habits before treatment enable medical staff to provide more individual, precise and complex care to patients, taking into consideration their nutritional status. The aim of this study was, therefore, to evaluate dietary habits related to lung cancer risk of lung cancer patients in comparison with controls from the Lower Silesia region of Poland. Material and methods Assessments of dietary habits, based on a validated questionnaire related to lung cancer risk were performed on 92 lung cancer patients and compared with the results obtained in 157 controls. Dietary patterns were evaluated concerning on eating frequency of high- and low- glycemic index products, vegetables and fruits, vegetable and fruit juices, green tea, liquid dairy products, meat and fried products over the previous year. Alcohol consumption was assessed on a dichotomous scale (yes or no). Results Majority of patients had inappropriate dietary habits, such as low consumption of low GI cereal products, vegetables, fruit and green tea, and a high consumption frequency of fried products. Conclusions Reported dietary mistakes indicate the need for dietary education among people at lung cancer risk and with newly diagnosed disease, to enhance their nutritional status.

Correlations between osteoprotegerin serum levels and body composition parameters in patients with sleep apnea syndrome and the possible influence on cardiovascular risk

INTRODUCTION Osteoprotegerin (OPG) is a member of the tumor necrosis factor family and a key regulator in bone turnover; it plays a role in the development of many cardiovascular diseases and may be treated as a marker of vascular damage. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition. The aim of the study was to evaluate correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk. MATERIAL AND METHODS A total of 125 patients with newly diagnosed OSA were enrolled in the study (including 34 females). The mean age was 54.48±8.81 years, mean AHI 33.16±20.44/h and mean BMI 33.76±7.18. A control group comprised 59 healthy subjects with mean age of 51.27±12.97 years and mean BMI 29.47±5.42. All subjects underwent a nocturnal respiratory polygraphy and body composition measurements were taken with bioelectrical impedance analysis. OPG serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS In OSA patients OPG correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while there was a positive correlation between osteoprotegerin and fat mass percentage (FM%). We demonstrated higher OPG serum levels in OSA patients with cardiovascular diseases than in those without comorbidities (4.01 vs 3.46pmol/l, p<0.05). CONCLUSION Our findings, combined with previous observations in other diseases, suggest that elevated OPG serum levels together with selected body composition parameters may be helpful in identifying OSA patients with increased cardiovascular risk.

Systemic redox status in lung cancer patients is related to altered glucose metabolism

Altered systemic redox status is often observed in lung cancer. However, detailed information on factors other, than smoking, which influence this perturbation is rather scarce. Elevated oxidative stress has been linked with disturbances in glucose metabolism before, but such associations have not been investigated in lung cancer. The aim of this study was to evaluate the relationship between systemic parameters of glucose metabolism and redox status in lung cancer patients (LC). Biochemical variables related to circulating glucose, i.e. glucose, insulin, c-peptide, fructosamine (FA), and glucose metabolism, i.e. β-hydroxybutyrate (BHB), lactate (LACT), non-esterified fatty acids (NEFAs), as well as redox status i.e. total antioxidant status (TAS) and total oxidant status (TOS) were determined for LC (n = 122) and control subjects (CS) (n = 84). HOMA-IR and the oxidative stress index (OSI) were calculated. LC patients had an altered redox status and glucose metabolism compared to CS. Positive correlations in LC were observed between TOS, OSI and circulating glucose as well as FA, while TAS positively correlated with BHB and NEFAs. In contrast, in metastatic LC, NEFAs and BHB positively correlated with OSI. Smoking status additionally stratified the observed relationships. In conclusion, we found that parameters related to circulating glucose or non-enzymatic glycation were correlated with oxidative stress (TOS and OSI), while metabolites such as BHB and NEFAs were correlated with antioxidant capacity (TAS). Metastasis prevalence and smoking seem to influence these correlations. However, the detailed mechanism of this relationship requires further research, in particular as regards the surprising positive correlation between NEFAs and TAS.

Decreased sL-selectin serum levels in sleep apnea syndrome patients with cardiovascular diseases

BACKGROUND Obstructive sleep apnea syndrome (OSA) is a common disorder associated with an increased risk of cardiovascular diseases. OBJECTIVES sL-selectin is an adhesion molecule released from the surface of leukocytes as they are activated and may inhibit leukocyte attachment to the endothelium. The aim of this study was to evaluate sL-selectin serum levels in OSA patients with cardiovascular diseases. MATERIAL AND METHODS A total of 163 OSA patients were enrolled in the study. The mean age was 55.41 ± 8.63 years and the mean AHI (apnea hypopnea index) was 35.02 ± 22.28/h. A control group was composed of 59 healthy subjects. All subjects underwent a nocturnal respiratory polygraphy. sL-selectin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS sL-selectin serum levels were significantly lower in OSA patients than in the control group (1080.02 ± 175.29 vs 1350.73 ± 569.75 ng/mL, p < 0.05). In addition, there was a negative correlation between sL-selectin levels and AHI and DI and a positive correlation between sL-selectin levels and mean and minimum saturation. sL-selectin levels were lower in OSA patients with cardiovascular diseases than in those without co-morbidities. We also found that sL-selectin correlated positively with HDL-cholesterol (high density lipoprotein) and negatively with uric acid and CRP (C-reactive protein). CONCLUSIONS Our work, together with observations relating to other diseases and experimental studies, suggests that lower sL-selectin levels could play a role in an increased risk of cardiovascular complications in sleep apnea syndrome. However future studies are needed to understand the role of sL-selectin in sleep apnea syndrome.