Long non-coding RNA MIR205HG regulates KRT17 and tumor processes in cervical cancer via interaction with SRSF1.

Abnormal expression of long non-coding RNAs (lncRNAs) has been demonstrated to be a vital regulatory factor in a large number of malignancies. The investigation in cervical cancer and the associated modulation mechanisms are yet to be probed. The aim of this study is to specifically investigate the expression pattern and modulatory mechanism of MIR205HG in cervical cancer. Our paper firstly revealed the up-regulation of KRT17 in cervical cancer. Function assays further displayed that KRT17 silencing impaired the proliferation and migration, and activated the apoptosis of cervical cancer cells. Based on the finding that MIR205HG could regulate KRT17 expression, we further probed the detailed mechanism between MIR205HG and KRT17. It was observed from mechanism experiments that MIR205HG depleted SRSF1 to increase KRT17 expression. The whole mechanism of MIR205HG/SRSF1/KRT17 axis affecting cell proliferation, apoptosis and migration in cervical cancer was validated using rescue assays. In conclusion, MIR205HG modulated the biological activities of cervical cancer cells via targeting SRSF1 and regulating KRT17, which better understood the pathogenesis of cervical carcinoma and excavated a novel therapeutic target.

Development of serum parameters panels for the early detection of pancreatic cancer.

Early detection of pancreatic cancer is promising for improving clinical outcome; however, no effective biomarker has yet been identified. Here, we detected 61 clinical serum parameters in 200 healthy controls (Ctrls), 163 pancreatic ductal adenocarcinoma (PDAC) patients and 109 benign pancreatitis patients (Benign) in the training group. A metropolis algorithm with Monte Carlo simulation was used for identifying parameter panels. Sera from 183 Ctrl, 129 PDAC and 95 Benign individuals were used for cross-validation. Samples from 77 breast, 72 cervical, 101 colorectal, 138 gastric, 108 prostate and 132 lung cancer patients were collected for evaluating cancer selectivity. A panel consisting of carbohydrate antigen (CA)19-9, albumin (ALB), C-reactive protein (CRP) and interleukin (IL)-8 had the highest diagnostic value for discriminating between PDAC and Ctrl. The sensitivity (SN) was 99.39% for all-stage, 96.10% for early-stage and 98.80% for advanced-stage PDAC at 90% specificity (SP). In the validation group, the sensitivities were 93.80, 93.10 and 94.40%, respectively, at 90% SP. This panel also identified 80.52% of the breast cancer, 66.67% cervical cancer, 86.14% colorectal cancer, 89.86% gastric cancer, 71.30% prostate cancer and 93.85% lung cancer samples as non-PDAC. The panel consisting of CA19-9, carbon dioxide, CRP and IL-6 panel had the highest diagnostic value for discriminating between PDAC and Benign. The SN was 74.23% for all-stage, 75.30% for early-stage and 74.40% for advanced-stage PDAC at 90% SP. In the validation group, the sensitivities were 72.10, 76.10 and 67.20%, respectively, at 90% SP. Our parameter panels may aid in the early detection of PDAC to improve clinical outcome.

Genes expression profiling of peripheral blood cells of patients with hepatocellular carcinoma.

HCC (hepatocellular carcinoma) is often diagnosed at an advanced stage with poor prognosis. Peripheral blood may be useful in cancer classification, and therefore we investigated the gene expression found by Affymetrix HG-U133 Plus2.0 microarray, with samples from nine HCC patients and five healthy NC (normal controls). A total of 726 probe sets showed significant differences based on the criteria of P<0.05 and absolute fold change >2. The genes were related to many biological functions, including immune response, transcription regulation and metabolism processes. Ten genes [IL-8 (interleukin 8), GOS2 (G0 /G1 switch gene 2), CXCR4 (CXC chemokine receptor 4), FOS, RPS24 (40S ribosomal protein S24), HAP90AA1, PFDN5, RPL27, GZMA and PFN1] showing significant differences were confirmed by real-time PCR in 54 HCC patients and 56 healthy NC. Seven genes [IL-8, GOS2, CXCR4, FOS, RPS24, HSP90AA1 (heat shock protein 90AA1) and PFN1] showed significant difference both in RT-PCR (reverse transcription-PCR) and microarray. Expression of IL-8 and FOS proteins was up-regulated in HCC compared with healthy controls. A gene signature in peripheral blood which can distinguish HCC patients and healthy controls may have been identified.

A novel differential diagnostic model based on multiple biological parameters for immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis in China. An accurate diagnosis of IgAN is dependent on renal biopsies, and there is lack of non-invasive and practical classification methods for discriminating IgAN from other primary kidney diseases. The objective of this study was to develop a classification model for the auxiliary diagnosis of IgAN using multiparameter analysis with various biological parameters. METHODS: To establish an optimal classification model, 121 cases (58 IgAN vs. 63 non-IgAN) were recruited and statistically analyzed. The model was then validated in another 180 cases. RESULTS: Of the 57 biological parameters, there were 16 parameters that were significantly different (P < 0.05) between IgAN and non-IgAN. The combination of fibrinogen, serum immunoglobulin A level, and manifestation was found to be significant in predicting IgAN. The validation accuracies of the logistic regression and discriminant analysis models were 77.5 and 77.0%, respectively at a predictive probability cut-off of 0.5, and 81.1 and 79.9%, respectively, at a predictive probability cut-off of 0.40. When the predicted probability of the equation containing the combination of fibrinogen, serum IgA level, and manifestation was more than 0.59, a patient had at least an 85.0% probability of having IgAN. When the predicted probability was lower than 0.26, a patient had at least an 88.5% probability of having non-IgAN. The results of the net reclassification improvement certificated serum Immunoglobulin A and fibrinogen had classification power for discriminating IgAN from non-IgAN. CONCLUSIONS: These models possess potential clinical applications in distinguishing IgAN from other primary kidney diseases.

Increased thyroid function and elevated thyroid autoantibodies in pediatric patients with moyamoya disease: a case-control study.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate whether thyroid function and thyroid autoantibodies were associated with the risk of moyamoya disease in pediatric subjects. METHODS: Thyroid function and thyroid autoantibodies were evaluated in patients with moyamoya disease and control subjects, and their associations with moyamoya disease were estimated using multivariate analysis. RESULTS: We included 114 pediatric patients and 114 healthy control subjects. The patients displayed higher prevalence of increased thyroid function and elevated thyroid autoantibodies in comparison with control subjects. These remained significant after multivariate adjustment; the ORs (95% CI) for increased thyroid function and evaluated thyroid autoantibodies were evaluated as 12.47 (1.55 to 100.51) and 4.33 (1.29 to 14.59), respectively. CONCLUSIONS: Increased thyroid function and elevated thyroid autoantibodies are associated with moyamoya disease and therefore monitoring of thyroid function and thyroid autoantibodies in patients with moyamoya disease is suggested, which might help to guide subsequent clinical management.

Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases.

We have investigated the changing rule of serum form of GP73 (sGP73) in different hepato-pathologic processes and identified the sGP73 role in inflammation, fibrosis and carcinogenesis since sGP73 has been regarded as a candidate tumor marker. Quantitative enzyme-linked immunosorbent assay detected sGP73 in 535 subjects with hepatocellular carcinoma (HCC), liver cirrhosis (LC), hepatitis, focal nodular hyperplasia (FNH), angioma, intra-hepatic cholangio-carcinoma (ICC) and metastatic cancer from adenocarcinomas (MC). Median sGP73 in LC was higher than in HCC and hepatitis (p = 0.001), and sGP73 in all three groups were higher than those in healthy individuals (p < 0.001); sGP73 in LC patients with Child-Pugh class A was lower than in class B and C (p = 0.001), no significant difference was found between early and advanced HCC groups (110.4 µg/L vs. 102.8 µg/L). AFP/GP73 had a sensitivity of 75.8% and specificity of 79.7% with an area under the receiver operating curve (AUROC) of 0.844 vs. 0.812 for AFP (p = 0.055) with a sensitivity of 95.2% and specificity of 47.1%; in detecting early HCC, AUROC of AFP/GP73 was 0. 804 vs. 0.766 for AFP (p = 0.086). sGP73 correlated with AST, AST/ALT, ALB, A/G and ALP in LC. The positive rate of sGP73 in angioma, FNH, ICC, and MC was 0, 50, 63.3, 53.3%, respectively; AFP/GP73 was 0.796 with the sensitivity of 81.4% and specificity of 70.0% when differentiating MC from AFP-negative HCC. Increased sGP73 is related to hepatic impairment and chronic fibrosis, and when combined with AFP could improve the differential diagnosis of hepatic diseases.

Association of a functional polymorphism in the MMP-3 gene with Moyamoya Disease in the Chinese Han population.

BACKGROUND: Moyamoya disease (MMD) is an uncommon cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. The important role of genetic factors in the etiology and pathogenesis of MMD is being increasingly recognized. The study was designed to examine the association of single nucleotide polymorphisms in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) genes with MMD occurrence. METHODS: A case-control study was performed. Five functional promoter polymorphisms in the MMP-2, MMP-3, MMP-9 and MMP-13 genes and a potentially functional promoter polymorphism in the TIMP-2 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. Their associations with MMD were analyzed by multivariate logistic regression. RESULTS: In total, 208 definite patients with MMD (including 31 familial MMD, FMMD, patients) and 224 healthy subjects were recruited. The frequency of the MMP-3 5A/6A and 5A/5A genotypes was significantly lower in MMD patients (OR = 0.57, 95% CI 0.38-0.86, p(corr) = 0.042) compared with healthy controls in a dominant genetic model. Significant differences of the MMP-3 5A/6A polymorphism were also detected between FMMD patients and controls both in the dominant genetic model (OR = 0.23, 95% CI 0.08-0.68, p(corr) = 0.048) and the additive genetic model (OR = 0.24, 95% CI 0.08-0.69, p(corr) = 0.048). CONCLUSION: The functional polymorphism in the MMP-3 promoter might be associated with susceptibility to both MMD and FMMD in the Chinese Han population. The findings need to be validated in further studies including more subjects from different populations.

Application of a multiplex SNP genotyping system in predicting genetic susceptibility to CAD in Chinese people of Han ethnicity.

BACKGROUND: Coronary artery disease (CAD) is a multifactorial disease influenced by various genetic factors involved in accumulation of atherosclerosis in the walls of the coronary arteries. Many single nucleotide polymorphisms (SNPs) are associated with CAD. MATERIAL/METHODS: DNA samples were extracted from peripheral white blood cells and 32 tag SNPs of 12 genes (ADD1, PECAM-1, CRP, ecNOS, PC-1, SELL, GNB3, ACE, AT1R, AGT, MTHFR and HL) that were listed in International Haplotype Map (hapmap) for Chinese people of Han ethnicity in Beijing (CHB) were selected for use in the current work. Genotypes of SNPs were investigated with the Genome Lab SNP stream genotyping system after polymerase chain reaction, extension and hybridization were performed. The levels of the biochemical index were detected with the Roche 7600 automatic biochemical modular system. RESULTS: The genotype and/or allele frequencies of 6 tag SNPs in CRP, ecNOS, PC-1 and ACE genes were significantly different between CAD and control groups. According to the linkage-disequilibrium levels of SNPs, the haplotypes were constructed and the results showed that the frequencies of the constructed haplotypes of ecNOS, PC-1 and ACE genes were associated with CAD. Genotypes of CRP and ACE genes were associated with serum CRP and ACE levels. CONCLUSIONS: Six SNPs that were discovered and were associated with CAD may help in explaining the molecular basis of the disorder and the susceptibility to coronary atherosclerosis. It can also help identify early prediction, prevention and therapy for CAD.

Association between the interleukin-6 gene -572G/C and -597G/A polymorphisms and coronary heart disease in the Han Chinese.

BACKGROUND: Recent studies have shown that elevated plasma interleukin-6 (IL-6) levels in coronary heart disease (CHD) patients are associated with polymorphisms in the promoter region of the IL-6 gene. However, related studies of these phenomenon are rare in the Han population of China. The aim was to develop a rapid IL-6 gene genotyping assay by fluorescent resonance energy transfer (FRET) and melting curves on a LightCycler system and then study the association between IL-6 gene polymorphisms and CHD. MATERIAL/METHODS: Two hundred thirty-one CHD patients and 210 controls, all of Han ethnicity from northern China, were analyzed by the established method. DNA sequencing analysis confirmed the results. RESULTS: Three genotypes were found for the -572G/C polymorphism in the Han Chinese. Statistical analysis for the this polymorphism revealed a significant difference between G allele carriers (GG+GC) and non-G allele carriers (CC) in both the CHD and the control group. Ten cases were identified to be of GA genotype for the -597G/A polymorphism in the Han Chinese. PCR product sequencing confirmed all the results. CONCLUSIONS: A rapid IL-6 gene genotyping assay was developed. The clinical data revealed that the -572G/C polymorphism in the IL-6 gene promoter region is involved in the pathogenesis and progression of CHD in the Han Chinese.

A study of health effects of long-distance ocean voyages on seamen using a data classification approach.

BACKGROUND: Long-distance ocean voyages may have substantial impacts on seamen's health, possibly causing malnutrition and other illness. Measures can possibly be taken to prevent such problems from happening through preparing special diet and making special precautions prior or during the sailing if a detailed understanding can be gained about what specific health effects such voyages may have on the seamen. METHODS: We present a computational study on 200 seamen using 41 chemistry indicators measured on their blood samples collected before and after the sailing. Our computational study is done using a data classification approach with a support vector machine-based classifier in conjunction with feature selections using a recursive feature elimination procedure. RESULTS: Our analysis results suggest that among the 41 blood chemistry measures, nine are most likely to be affected during the sailing, which provide important clues about the specific effects of ocean voyage on seamen's health. CONCLUSIONS: The identification of the nine blood chemistry measures provides important clues about the effects of long-distance voyage on seamen's health. These findings will prove to be useful to guide in improving the living and working environment, as well as food preparation on ships.

[Comparison of serum biochemical features between SARS and other viral pneumonias].

OBJECTIVE: To identify blood chemistry changes in coronavirus of severe acute respiratory syndrome (SARS). METHODS: Biochemical changes in SARS patients were summarized and compared with other viral pneumonias. Serum total protein (TP), albumin (Alb), total cholesterol (TC), triglyceride (TG), calcium (Ca), ferrum (Fe), lactate dehydrogenase (LDH), creatine kinase (CK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between SARS and other viral pneumonias were examined by Roche Diagnostics assay, HITACHI7600 automatic analyzer. Clinically confirmed SARS patients, patients with other viral pneumonias, and healthy controls were included in the study. RESULTS: Compared with healthy person, the levels of serum TC, Fe, Ca, Alb were significantly lowered (P<0.05 or P<0.01), while the activity of LDH, CK, ALT, AST were elevated, the increase of CK and the decrease of Fe were the most significant (P<0.05 or P<0.01), the changes of TP and TG were not obvious. In the other viral pneumonias patients, ALT, AST, LDH were elevated slightly than those of healthy person, while Fe, Ca, Alb, TC, CK were a little reduced, but there was no significant difference between the two groups. In convalescent stage, all the tests were returned to normal ranges except ALT, AST were still elevated in SARS patients. CONCLUSION: The changes in serum biochemistry are more marked in SARS patients compared with patients suffering from other viral pneumonias, the decrease of Fe as well as the inhibition of TC may be caused by the treatment of anti-virus.

[Experimental study of the effects of mild hypothermia on the acute myocardial infarction size in the rabbits with coronary artery reperfusion].

OBJECTIVE: To study the effect of mild hypothermia on the acute myocardial infarction size in the rabbits with coronary artery reperfusion. METHODS: fourteen rabbits were randomly divided into two groups: mild hypothermia group and control group. Each group underwent 45 minutes of left anterior descending coronary artery occlusion and 2 hours of reperfusion. Core temperatures were measured with thermistor. The mild hypothermia group received ice cooling around the body and the core temperature was dropped to 32-35 centigrade after occluded for 30 minutes, while the control group's body temperature were kept above 38 centigrade. The myocardial area at risk and the infarct area were determined with Evan's blue dye and triphenyl tetrazolium chloride (TTC). RESULTS: The total elevated amplitude of ST segment in chest leads V1, V3 and V5 in the mild hypothermia group was (25.8+/-8.5) mV, it was lower than that in the control group (37.7+/-6.5) Mv (P=0.021). The changes of serum MB isoenzyme of creatine kinase (CK-MB) activities in mild hypothermia group was (2646.9+/-1227.3) U/L, it was significantly lower than that in the control group (4787.8+/-1934.2) U/L(P=0.045). The weight of infarct myocardium of the mild hypothermia group was (0.23+/-0.05)g, it was lower than that in the control group (0.42+/-0.16)g (P=0.020). Myocardial infarct size as a percentage of the risk zone (0.214+/-0.044 vs. 0.357+/-0.066, P=0.001) and of the left ventricle weight (0.041+/-0.010 vs. 0.071+/-0.027, P=0.029) were smaller than those in the control group. The ratio of the survived myocardial area over the risk zone in the mild hypothermia group was significantly higher than that in the control group (0.786+/-0.044 vs. 0.643+/-0.066, P<0.001). CONCLUSION: Mild hypothermia may reduce infarct size in the rabbits with transient acute myocardial infarction, and increase survived myocardium in the risk zone.

[Studies of bi-derectional modulation effect of kudzuvine root on immunol cells].

OBJECTIVE: To evaluate bi-directional modulation effect of Chinese herbal medicine on immunol cells. METHOD: Two different active portions were isolated from Kudzuvine Root(Radix puerariae), one being the ethanol extraction and another the water extraction. Different concentration of these two different portions was studied by using PMA stimulated lymphocyte or eosinophil initiated chemiluminescence system. RESULT: Water extraction of Kudzuvine Root could enhance chemiluminescence concentration dependently whereas enthanol extraction of Kudzuvine Root inhibited the chemiluminescence significantly. CONCLUSION: The bi-directional regulation effect of Chinese herbal medicine can be found in the same herb, because of its efficacy of different active compounds.

Identification and characterization of novel serum microRNA candidates from deep sequencing in cervical cancer patients.

Small non-coding microRNAs (miRNAs) are involved in cancer development and progression, and serum profiles of cervical cancer patients may be useful for identifying novel miRNAs. We performed deep sequencing on serum pools of cervical cancer patients and healthy controls with 3 replicates and constructed a small RNA library. We used MIREAP to predict novel miRNAs and identified 2 putative novel miRNAs between serum pools of cervical cancer patients and healthy controls after filtering out pseudo-pre-miRNAs using Triplet-SVM analysis. The 2 putative novel miRNAs were validated by real time PCR and were significantly decreased in cervical cancer patients compared with healthy controls. One novel miRNA had an area under curve (AUC) of 0.921 (95% CI: 0.883, 0.959) with a sensitivity of 85.7% and a specificity of 88.2% when discriminating between cervical cancer patients and healthy controls. Our results suggest that characterizing serum profiles of cervical cancers by Solexa sequencing may be a good method for identifying novel miRNAs and that the validated novel miRNAs described here may be cervical cancer-associated biomarkers.

Clinical evaluation of the levels of 12 cytokines in serum/plasma under various storage conditions using evidence biochip arrays.

Cytokines are a group of peptides which form a sophisticated network to modulate multiple cellular events. Within such a network, and through complex feedback mechanisms, cytokine functions are largely interdependent and closely associated with a number of pathological processes. In the present study, the EVIDENCE 180 system was used to study the effects of storage temperature and repeated freeze/thaw cycles on the concentration of 12 cytokines in various sample types. Samples were collected from 9 healthy volunteers and stored by 3 methods: gel, glass and lithium heparin (LH) tubes. Immediately following collection, the concentration of each cytokine in the samples was measured. Cytokine concentrations of the 3 sample types that did not undergo repeated freeze/thaw cycles were compared with those subjected to 1­10 freeze/thaw cycles. In addition, the dynamic changes of 6 sample types which were stored at 4˚C for 6 h to 6 days was analyzed. In addition, the within­ and between­run precision of 12 cytokines on the biochip array was evaluated. Interleukin (IL)­8, vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) concentrations were lower in plasma compared with serum. Cytokine levels in serum and plasma were affected by several freeze/thaw cycles with IL­1ß, ­4 and ­10 increasing significantly following 1 freeze/thaw cycle and remaining at stable increased levels for the duration of the additional 9 cycles. In separated serum samples in gel and glass tubes stored at 4˚C for 6 days, no difference in concentration of the 12 cytokines was identified. In the other 4 sample types, IL­8, VEGF, tumor necrosis factor α and EGF levels were altered when stored at 4˚C. Results indicate that the EVIDENCE 180 system is stable and plasma was observed as the best sample type to determine concentration of the 12 cytokines using this biochip array. Repeated freeze/thaw cycles and storage at 4˚C was identified to affect the concentration of the 12 cytokines. The current study demonstrates that repeated freeze/thaw cycles of samples must be avoid. In addition, results indicate that plasma or serum must be separated immediately following centrifugation and sample concentration should be measured as soon as possible.

Impact of chronic kidney disease on serum tumor markers concentrations.

BACKGROUND: Serum tumor markers have always been of clinical importance in the diagnosis, monitoring disease progression and therapy efficacy for patients with malignant diseases. However, elevated serum tumor markers are found in some benign conditions, especially in chronic kidney disease (CKD). The elevation of them in CKD might cause confusion and misuse of these tumor markers. We conducted this retrospective study to investigate which of the five widely used tumor markers including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) are affected markedly by CKD, in order to use them more effectively. METHODS: Serum tumor marker concentrations, biochemical, hematological parameters, and urinalysis were measured in CKD patients and healthy controls. The positive rate and median tumor markers' level in CKD patients and controls, and those in CKD patients stratified by CKD grade were compared using nonparametric rank tests. Correlation analysis of serum tumor markers and other parameters in CKD patients were performed using the Spearman correlation coefficient. Multivariate Logistic regression analysis was used to estimate the important variables that caused elevated serum concentrations of these markers in CKD patients. RESULTS: The overall positive rates and serum concentrations of Cyfra21-1, SCC, CEA in CKD group were significantly higher than those in control group. Positive rate and serum concentrations of those tumor markers increased as kidney function decreased. Both univariate analysis and multivariate regression analysis showed that the elevations of those tumor markers were not only associated with kidney function, but also with nutritional status. CONCLUSIONS: Serum concentrations of Cyfra21-1, SCC, CEA are significantly influenced by kidney function, as well as nutritional status. Therefore, in clinical work, the indices of kidney function and nutritional status could be simultaneously measured to improve interpretation of the results of those tumor marker concentrations.

Prognostic value of combined serum biomarkers in predicting outcomes in cervical cancer patients.

BACKGROUND: We evaluated the prognostic value of pretreatment serum biomarkers in predicting outcomes in cervical cancer patients subjected to treatment. METHODS: Serum samples collected from 60 cervical cancer patients and 60 age-matched healthy individuals were used for the detection of 22 biomarkers, prior to therapy. Cox multivariate analysis and classification and regression tree analysis (CART) were performed to evaluate the prognostic factors. RESULTS: Cox multivariate analysis disclosed that carbohydrate antigen 153 (CA153), squamous cell carcinoma antigen (SCC) and tumor necrosis factor-α (TNF-α) are associated with prognosis in cervical cancer. CART analysis led to the stratification of patients into 3 groups: (1) serum concentrations of CA153 ≥17.60 µg/l, (2) serum concentrations of CA153 <17.60 µg/l and TNF-α ≥10.60 pg/ml, and (3) serum concentrations of CA153 <17.60 µg/l and TNF-α <10.60 pg/ml. The 2-y overall survival rates for Groups 1, 2 and 3 were 33.3%, 60.0% and 93.9%, respectively. CONCLUSIONS: Higher serum concentrations of TNF-α, SCC and CA153 before therapy are independently associated with poor prognosis in patients with stage I and II disease. Combined usage of these three biomarkers allows efficient evaluation of outcomes in cervical cancer patients.

The Use of Principal Component Analysis in MALDI-TOF MS: a Powerful Tool for Establishing a Mini-optimized Proteomic Profile.

BACKGROUND: Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) technology has been applied to the exploration of biomarkers for early cancer diagnosis, but more effort is required to identify a single sensitive and specific biomarker. For early diagnosis, a proteomic profile is the gold standard, but inconvenient for clinical use since the profile peaks are quantitative. It would therefore be helpful to find a minimized profile, comprising fewer peaks than the original using an existing algorithm and compare it with other traditional statistical methods. METHODS: In the present study, principal component analysis (PCA) in the ClinProt-Tools of MALDI-TOF MS was used to establish a mini-optimized proteomic profile from gastric cancer patients and healthy controls, and the result was compared with t-test and Flexanalysis software. RESULTS: Eight peaks were selected as the mini-optimized proteomic profile to help differentiate between gastric cancer patients and healthy controls. The peaks at m/z 4212 were regarded as the most important peak by the PCA algorithm. The peaks at m/z 1866 and 2863 were identified as deriving from complement component C3 and apolipoprotein A1, respectively. CONCLUSIONS: PCA enabled us to identify a mini-optimized profile consisting of significantly differentiating peaks and offered the clue for further research.

Identification of potential predictors for subtype IgA nephropathy through analyses of blood biochemical indicators.

BACKGROUND: Immunoglobulin A nephropathy (IgAN), a dominant glomerulonephritis in China, has presented challenges in its early non-invasive diagnosis and accordingly has drawn considerable attention regarding the need to develop effective easy-to-conduct methods. METHODS: In this retrospective study, a support vector machine-based classifier was trained to obtain a minimum subset with the highest discerning power between IgAN and non-IgAN cases in China based on 36 biochemical indicators connected with a feature-selection procedure. RESULTS: Our analyses indicated 19 biochemical indicators with differential distributions between IgAN and non-IgAN cases, indicating their potential as classifiers. Further examination for the discerning power of all k-feature combinations indicated a 5-feature combination, ALB+CK+Cr+HDL+CA125+TB, which gave the best accuracy, 79.71%, in classifying all training data into the 2 subtypes of nephropathy. Moreover, two combinations, ALB+CK+AFP+AST and TP+Glu+DB+CH, were gender-specific, giving the best classification accuracies of 81.90% and 80.22% for male and female patients, respectively. These 3 classifiers achieved classification accuracies of 75.36%, 72.00% and 84.09% in the entire, the male and the female independently validated datasets, respectively. CONCLUSIONS: Blood biochemical indicators could distinguish between IgAN and non-IgAN cases with a bioinformatic algorithm, providing a promising method to diagnose the subtypes of nephropathy.

[Feasibility of peptide mass fingerprinting for differential diagnosis of IgA and non-IgA nephropathy].

OBJECTIVE: To investigate the feasibility of peptide mass fingerprinting for non-invasive differential diagnosis of IgA nephropathy (IgAN) from the non-IgA nephropathy (IgAN).? METHODS: According to the results of renal biopsy, 56 patients were divided into IgAN group (n=28) and non-IgAN group (n=28), and peptide mass fingerprints were acquired from these patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: Nine different peptides were identified between IgAN and non-IgAN. The two most distinctive differentially expressed peptides, with peptide peak values of 4476.46 and 1968.10, showed area under curve values of 86.18% and 79.77%. Principal component analysis demonstrated that the accumulated explained variance of the first 8 differential peptides reached 95%, suggesting the feasibility of differential diagnosis of IgAN from non-IgAN. Comparison with the Matrix protein database identified the peptide with a relative molecular mass of 5338.08 as a fragment of mucin 4 inform and the 2082.77 peptide as fragment of α1-II type collagen inform. CONCLUSION: MALDI-TOF MS is feasible for differential diagnosis of IgAN and non-IgAN and also has great potentials in the classification of the subtypes of other systemic diseases.