The Association between Echocardiographic Parameters of Heart Failure with Preserved Ejection Fraction and Fluid Status Biomarkers in Hemodialysis Patients.

Overhydration and cardiac function abnormalities are common in hemodialysis patients. The association of N-terminal prohormone for brain natriuretic peptide (NT-proBNP) and other fluid status biomarkers with echocardiographic parameters of heart failure with preserved ejection fraction (HFpEF) is scarcely investigated in this population. A total of 100 separate measurements performed in 50 dialysis patients (29 male, aged 60 ± 17 years) in NYHA class II/II and preserved left ventricle ejection fraction were analyzed. Plasma levels of NT-proBNP, mid-regional prohormone for atrial natriuretic peptide (MR-proANP) and copeptin (CPP) were measured. The E/e' ratio as an index of HFpEF and other echocardiographic parameters were calculated. An E/e' ratio >9 was associated with higher median right ventricular systolic pressure (RVSP) and LVMI values. Left atrium volume index (LAVI) as well as NT-proBNP and MR-proANP, but not CPP levels were significantly higher in this group. In a stepwise multivariate analysis, only CPP and IL-6 levels were found to be independently associated with the E/e' ratio in the study group, whereas NT-proBNP and MR-proANP were associated only with left heart structure parameters and LVEF. Of the analyzed biomarkers, only the CPP level was found to be independently associated with the E/e' ratio in maintenance hemodialysis patients.

Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer.

Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly increased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with a reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Furthermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7 × 10-5) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.

Blood serum proteins as biomarkers for prediction of survival, locoregional control and distant metastasis rate in radiotherapy and radio-chemotherapy for non-small cell lung cancer.

BACKGROUND: Several studies have documented that blood biomarkers can improve basic prognostic models in radiotherapy and radio-chemotherapy for non-small cell lung cancer. The current study evaluated the prognostic impact of six markers focusing on their utility in homogenous subsets, compared to the significance in a large heterogeneous group. METHODS: Blood samples of 337 patients who were referred for curative or palliative external beam thoracic radiotherapy for non-small cell lung cancer were collected. The concentration of osteopontin (OPN), vascular endothelial growth factor (VEGF), erythropoetin (EPO), high mobility group box 1 protein (HMGB1), insulin-like growth factor 1 (IGF-1) and platelet-derived growth factor (PDGF) in serum were measured by ELISA assay and the prognostic potential was assessed using univariable and multivariable survival models. RESULTS: Multivariable analysis revealed that out of several variables studied six dichotomized features: namely: cigarette smoking, lack of chemotherapy, palliative doses of radiotherapy, high OPN concentration, advanced T stage and high VEGF concentration had a highly significant (p < 0.005) and independent influence on overall survival in the group of 337 patients. In a subset of patients treated with curative radio-chemotherapy or radiotherapy (N = 148) tumor pathology, EPO concentration and VEGF concentration, significantly and independently influenced overall survival. In a subset of patients with squamous cell cancer (N = 206) OPN had a highly significant impact on overall survival. In contrast, in a subset of patients with nonsquamous histology (N = 131) only VEGF had a significant influence on survival. CONCLUSIONS: Blood serum proteins appear to be clinically useful prognosticators of overall survival in radio-chemotherapy and radiotherapy for non-small cell lung cancer. In unselected heterogeneous groups, dichotomized concentrations of OPN and VEGF emerged among the strongest independent prognosticators of overall survival. VEGF and EPO concentration (dichotomized) were found to be independent prognostic factors among the patients treated with curative doses of radiotherapy. The utility of OPN as a prognostic marker appeared restricted to the patients with squamous histology.

Early diagnosis of radiotherapy failure for patients with head and neck cancer: the role of biochemical markers.

PURPOSE: There is a lack of effective diagnostic tools for early assessment of radiotherapy (RT) outcome in patients with head and neck cancer (HNC). The timely diagnosis of treatment failure may facilitate use of salvage procedures to prevent disease progression. We assessed squamous cell carcinoma antigen and CYFRA 21-1 as early markers of radiotherapy failure in patients with HNC. METHODS: Between January 2009 and February 2012, 185 patients (median age 59 years) with squamous cell carcinoma were treated with curative intent with RT alone or combined with chemotherapy (ChT). Markers were estimated in the serum 2 times: before RT and after completion of treatment. RESULTS: The median of follow-up was 40 months. Locoregional control (LRC) was 53% and locoregional failure (LRF) was 31%. When comparing LRC and LRF, there were no significant differences between markers concentration obtained before RT. After RT, CYFRA 21-1 (p = 0.018) was significantly elevated in the LRF group. Patients with CYFRA 21-1 <1.79 ng/mL had a higher disease-free survival rate compared to patients with CYFRA 21-1 ≥1.79 ng/mL (74% vs 53%, respectively). After RT, CYFRA 21-1 was significantly related to the overall survival ratio in both univariate (p = 0.049) and multivariate analysis (p = 0.019). CONCLUSIONS: CYFRA 21-1 assessed at the end of RT or ChT seems to be a prognostic marker for tumor response. A high concentration of CYFRA 21-1 after treatment increases the risk of death. CYFRA 21-1 might be suggested in the monitoring of carcinomas of HNC.

[Usefulness of osteopontin (OPN) determinations in ovarian cancer patients who underwent first-line chemotherapy]. / Przydatnosc oznaczen stzenia osteopontyny (OPN) u chorych na raka jajnika poddanych chemioterapii I rzutu.

INTRODUCTION: Currently CA 125 is a marker of choice for monitoring ovarian cancer Nonetheless, scientists are still searching for new markers, which could provide additional information for the evaluation of treatment, especially in patients with normal CA 125 levels, despite the progression of the disease. According to the latest reports, OPN can be a potential new marker: AIM: Estimation of usefulness of OPN determinations in the monitoring of ovarian cancer patients. MATERIAL AND METHODS: The study included 54 ovarian cancer patients, undergoing chemotherapy Markers were measured before, during and after treatment. The dynamics of the change of OPN levels was shown on line graphs, using Microsoft Excel programme. Statistical analysis was performed by Kaplan-Meier method and log-rank test. RESULTS: 44% of patients from the study group were found to have low CA 125 levels. In these cases only the increase of OPN concentration indicated recurrence of the disease. In 43% of patients the high initial CA 125 and OPN levels decreased during chemotherapy and complete regression was stated in these patients. Nevertheless, in 13/17 patients a repeated increase of OPN concentration signalling the recurrence, earlier than CA 125 and clinical recurrence manifestation, was observed. In 13% of patients high initial levels of markers did not decrease during chemotherapy which correlated with the progression of the disease. Our study showed that only the CA 125 levels had a significant influence (p=0.00063) on the disease-free survival time. CONCLUSIONS: Our data suggest a potential usefulness of the OPN determinations in estimating ovarian cancer recurrence. Nonetheless, there was no correlation between the initial OPN concentration and the disease-free survival time.

Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer.

BACKGROUND: Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints) detected by mass spectrometry that reflect overall features of a specimen's proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. METHODS: Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women). Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high-molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. RESULTS: We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions) that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity). Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0.0003) increased level of osteopontin in blood of the group of cancer patients studied (however, the plasma level of osteopontin classified cancer samples with 88% sensitivity but only 28% specificity). CONCLUSION: MALDI-ToF spectrometry of serum has an obvious potential to differentiate samples between early breast cancer patients and healthy controls. Importantly, a classifier built on MS-based serum proteome patterns outperforms available protein biomarkers analyzed in blood by immunoassays.

[Usefulness of the SCC, CEA, CYFRA 21.1, and CRP markers for the diagnosis and monitoring of cervical squamous cell carcinoma]. / Przydatnosc oznaczania markerów: SCC, CEA, CYFRA 21.1 oraz CRP w diagnostyce i monitorowaniu plaskonablonkowego raka szyjki macicy.

OBJECTIVE: To determine the usefulness of the SCC, CEA, CYFRA 21.1, and CRP markers for the diagnosis and early monitoring after treatment completion in women diagnosed with cervical squamous cell carcinoma. MATERIAL AND METHODS: Serum of 140 patients with diagnosed cervical squamous cell carcinoma was investigated. The women with the advanced stage of cervical carcinoma (FIGO IIIB) were divided into two subgroups: with positive and negative outcomes of the treatment. Levels of SCC, CEA, CYFRA 21.1, and CRP were measured before the treatment and immediately after the completion of radiotherapy. Immunochemical methods were used to measure proteins in both serum and plasma samples. RESULTS: 75% of the markers measured were within the reference range for FIGO stage I. The marker levels rose with the clinical progression of the disease. The median levels of all markers and the CRP levels in both groups were compared before the treatment. Only in case of CEA a considerable variation between these groups was observed. Elevated levels of CRP were observed twice more often in patients with negative outcome of the treatment. After the treatment, a significant decrease in all marker levels was observed in patients with positive outcome when compared to the levels at the moment of the diagnosis. CONCLUSIONS: SCC, CEA and CYFRA 21.1 markers show low diagnostic sensitivity in early stages of the disease in women diagnosed with cervical squamous cell carcinoma. The concentration of markers measured before the treatment, particularly CEA, may prove to be of prognostic value for women diagnosed with advanced cervical cancer. Certain markers may prove useful in the assessment of the therapy used. Measuring the CRP before the treatment may aid the prognosis of response to treatment in these patients.

[Evaluation of selected serum protein markers as early detectors of ovarian cancer]. / Ocena mozliwosci wczesnej diagnostyki raka jajnika na podstawie oznaczen wybranych bialek surowicy.

OBJECTIVE: an attempt to determine the value of the simultaneous quantization of osteopontin (OPN), insulin-growth factor II (IGF II), leptin, prolactin and CA 125 for early detection of ovarian cancer. MATERIALS AND METHODS: Prospective study of 69 women including: 15 females with ovarian cancer; 33 females with benign ovarian neoplasm; 21 disease-free females; The levels of IGF II, prolactin, leptin and CA 125 were determined in serum, while the level of OPN was checked in plasma. RESULTS: The concentrations of IGF II, leptin and prolactin do not let us distinguish among disease-free females, females with ovarian cancer and those with benign ovarian neoplasms on the basis of biochemical markers. The comparison of OPN and CA 125 levels showed significant differences in the concentrations of the biomarkers between disease-free females and females with ovarian cancer, as well as between females with benign ovarian neoplasms and females with ovarian cancer. The ROC curves for two groups: disease-free females and females with ovarian cancer, proved the diagnostic value of OPN and CA 125. CONCLUSIONS: The simultaneous quantization of OPN, IGF II leptin and prolactin has not been proved useful for the early detection of ovarian cancer. Statistically significant increase of OPN & CA 125 levels was noted in case of women with ovarian cancer diagnosed through microscopic examination. The analysis of ROC curves showed comparable diagnostic usefulness of both markers. Quantization of OPN may have an additional value for treatment monitoring of women diagnosed with ovarian cancer but with concentration of CA 125 within the reference value.