Circulating glypican-4 is a new predictor of all-cause mortality in patients with heart failure.

BACKGROUND: Heart failure confers a high burden of morbidity and mortality. However, risk prediction in heart failure patients still is limited. Blood-based biomarkers hold promise to improve clinical risk assessment. Recently we have identified circulating glypican-4 (GPC4) as a significant predictor of mortality in coronary angiography patients and patients with peripheral artery disease. The impact of serum GPC4 on mortality in patients with heart failure is unknown and is addressed in this prospective cohort study. METHODS: We prospectively recorded all-cause mortality in 288 patients with heart failure. GPC4 levels were measured using an enzyme-linked immunosorbent assay at baseline. RESULTS: During the 24-month follow-up period, 28.1% (n = 81) of the patients died. Serum GPC4 significantly predicted all-cause mortality (hazard ratio (HR) per doublingof GPC4 = 3.57 [2.31-5.53]; P < 0.001). Subgroup analysis showed that GPC4 was significantly associated with all-cause mortality in patients with reduced ejection fraction (HR per doubling = 3.25 [1.75-6.04]; P < 0.001) as well as in those with preserved ejection fraction (HR per doubling = 3.07 [1.22-7.70]; P = 0.017). The association between serum GPC4 and all-cause mortality remained significant in multivariable Cox regression analysis correcting for traditional risk factors (P = 0.035). Results from C-statistics indicated an additional prognostic value of GPC4 relative to NT-proBNP for the prediction of two-year all-cause mortality (P = 0.030). CONCLUSION: Circulating GPC4 independently predicts all-cause mortality in patients with heart failure.

Coronary Event Risk Test (CERT) as a Risk Predictor for the 10-Year Clinical Outcome of Patients with Peripheral Artery Disease.

(1) Background: Ceramides are a new kind of lipid biomarker and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with a worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague, as addressed in the present study. (2)Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the Coronary Event Risk Test (CERT) score, which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). (3) Results: Kaplan-Meier survival curves revealed that the overall survival of patients decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that each one-category increase resulted in a 35% rise in overall mortality risk (HR = 1.35 [1.16-1.58]). Multivariable adjustment, including, among others, age, LDL-cholesterol, type 2 diabetes, and statin treatment before the baseline, did not abrogate this significant association (HR = 1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin treatment is significantly stronger in patients with a higher risk, according to CERT. (4) Conclusions: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.

Myricetin attenuates hypoxia-induced inflammation in human adipocytes.

BACKGROUND: Adipose tissue hypoxia plays a crucial role in the development of chronic low-grade systemic inflammation which has been associated with the pathogenesis of obesity-related diseases. Myricetin is a natural compound present in numerous plant-based foods with presumed anti-inflammatory and beneficial health effects. The impact of this flavonoid on hypoxia-induced expression of inflammatory adipokines and hypoxia-regulated pathways is unknown so far and has been addressed in the present study. METHODS: Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured with or without myricetin under normoxic and hypoxic conditions for varying time periods. The effect of hypoxia and myricetin on the expression of the investigated adipokines was measured by real-time RT-PCR. Western blot analysis was used for the detection of transcription factors involved in hypoxia-regulated pathways. RESULTS: Myricetin interfered in the hypoxia-induced regulation of adipokines and the underlying pathways, which are involved in transmitting the inflammatory response. It strongly repressed hypoxia-induced expression of apelin, leptin, chemerin, asprosin, and DPP-4 and HIF-1α accumulation in the nucleus was diminished. Furthermore, the activation of the key regulators in the inflammatory response NF-κB, Akt, and CREB was suppressed by myricetin under hypoxic conditions. Myricetin also decreased hypoxia-induced accumulation of the pro-tumorigenic transcription factors Snail and Slug in the nucleus. CONCLUSION: Taken together, our results indicated that myricetin regulated hypoxia-induced expression of adipokines and hypoxia-regulated pathways in human adipocytes. Our study therefore provided evidence of the anti-inflammatory effects of myricetin in hypoxia-treated human adipocytes.

Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients.

PURPOSE: Apolipoprotein M (APOM) is a plasma apolipoprotein closely involved with lipid metabolism and inflammation. In vitro studies suggest that APOM may also have a tumor-suppressive role in breast cancer. In the present study, we aimed to evaluate the impact of plasma APOM levels on the prognosis of breast cancer patients. METHODS: We measured APOM levels using an enzyme-linked immunosorbent assay in 75 patients with ER-positive/HER2-negative metastatic breast cancer. The endpoint was overall survival (OS) at 24 months. RESULTS: During the 24-month follow-up period, 34.7% of the patients died. Baseline APOM levels were significantly reduced in patients who deceased during follow-up compared to survivors (42.7 ± 14.5 µg/mL versus 52.2 ± 13.8 µg/mL; P = 0.003). Cox regression analysis showed a hazard ratio of 0.30 [95% confidence interval 0.15-0.61]; P < 0.001 per doubling of APOM levels. Correction for age, C-reactive protein, menopausal state, histology of the primary tumor, metastatic site, number of metastases, endocrine resistance, scheduled therapy line, and kind of scheduled therapy indicated that circulating APOM predicted OS independently of these parameters (HRper doubling = 0.23 [0.09-0.56; P = 0.001). CONCLUSIONS: Our study suggests that circulating APOM is significantly linked with reduced mortality in metastatic breast cancer patients.

Cell-free circulating RAS mutation concentrations significantly impact the survival of metastatic colorectal cancer patients.

PURPOSE: RAS mutations are predictors of an adverse outcome in EGFR-targeted therapies and have been proposed as prognostic biomarkers of survival in metastatic colorectal cancer (mCRC). The analysis of circulating tumor DNA from plasma samples, known as liquid biopsies, has indicated that the RAS mutation status may change over time, potentially affecting patients' prognosis. To further evaluate the clinical validity of RAS mutation retesting using liquid biopsies, we prospectively investigated the impact of the circulating quantitative RAS mutation status on the course of mCRC. METHODS: The present study included 81 consecutively recruited patients with mCRC. We used targeted next-generation sequencing of circulating cell-free DNA to determine and quantify plasma RAS mutation status. RESULTS: Patients with a RAS mutation detected by liquid biopsy (37%; n = 30) were at increased risk of death during the follow-up period compared to RAS wild-type patients. Patients with evidence of a RAS mutation in the primary tumor but a putative RAS mutation loss in plasma (28%; n = 11) showed a prolonged survival compared to patients with a preserved RAS mutation status. Also, circulating RAS mutation concentrations significantly affected the outcome: The mortality risk of patients with a high RAS mutation concentration increased fivefold compared to subjects with a putative RAS mutation loss or low RAS mutation concentration. CONCLUSION: Our results emphasize the clinical value of circulating RAS mutations in managing mCRC.

Circulating Glypican-4 Is a Predictor of 24-Month Overall Survival in Metastatic Breast Cancer.

INTRODUCTION: Endocrine treatment combined with CDK4/6 inhibitors is the preferred treatment strategy in patients presenting with ER-positive/HER2-negative breast cancer, but the clinical course remains highly variable among individual patients. There is an unmet need for prognostic or predictive biomarkers in this important group of patients. Recently, we have identified circulating glypican-4 (GPC4) as a new biomarker of inferior outcomes in patients with metastatic colorectal cancer. The impact of plasma GPC4 levels on the survival of breast cancer patients is unknown and has been addressed in the present study. METHODS: Our study included 47 patients with ER-positive/HER2-negative metastatic breast cancer prior to treatment with CDK4/6 inhibitors combined with endocrine therapy. The endpoint was overall survival (OS) at 24 months. GPC4 levels were measured in plasma using an enzyme-linked immunosorbent assay. RESULTS: Increased circulating GPC4 levels were significantly linked to advanced age, postmenopausal state, visceral metastases, and invasive lobular carcinoma. During the 2-year observational follow-up period, 25.5% of patients died. The area under the receiver operating characteristic curve (ROC-AUC) analysis revealed an AUC of 0.713 [0.555-0.871]; p = 0.029 for OS; and an optimal cutoff value of GPC4 for predicting OS of 4.77 ng/mL. No patient showing GPC4 values below this cutoff died during the observational period. Cox regression analysis showed a hazard ratio of 2.14 [95% confidence interval: 1.24-3.67]; p = 0.006 for one standard deviation change of plasma GPC4. CONCLUSIONS: Our study suggests circulating GPC4 as a significant predictor of poor survival in metastatic breast cancer patients.

Circulating syndecan-1 and glypican-4 predict 12-month survival in metastatic colorectal cancer patients.

Cell surface syndecans and glypicans play important roles in the development and prognosis of colorectal cancer (CRC). Their soluble forms from proteoglycan shedding can be detected in blood and have been proposed as new prognostic biomarkers in several cancer entities. However, studies on circulating syndecan-1 (SDC1) and glypican-4 (GPC4) in CRC are limited. We, therefore, evaluated the impact of plasma SDC1 and GPC4 on the prognosis of metastatic (m)CRC patients. The present study included 93 patients with mCRC. The endpoints were progression-free survival (PFS) and overall survival (OS) at 12 months. SDC1 and GPC4 levels were measured in plasma using enzyme-linked immunosorbent assays. Plasma levels of SDC1 and GPC4 were significantly correlated. Significant correlations of these two markers were also found with carcinoembryonic antigen (CEA). Kaplan-Meier curve analyses indicated that PFS and OS probabilities significantly decreased with increasing levels of SDC1 and GPC4, respectively. Multivariable Cox regression analyses showed that both markers were significantly associated with PFS and OS independently from clinicopathological characteristics including CEA. Respective adjusted hazard ratios (HR) together with corresponding 95% confidence intervals for one standard deviation change of SDC1 were 1.32 [1.02-1.84] for PFS and 1.48 [1.01-2.15] for OS. Adjusted HRs [95% confidence intervals] of GPC4 were 1.42 [1.07-1.89] for PFS and 2.40 [1.51-3.81] for OS. Results from area under the receiver operating characteristic curve analyses suggest that GPC4 and SDC1 add additional prognostic values to CEA for OS. In conclusion, we showed significant associations of circulating SDC1 and GPC4 with poor survival of mCRC patients.

Serum glypican-4 is associated with the 10-year clinical outcome of patients with peripheral artery disease.

BACKGROUND: Patients with peripheral artery disease (PAD) are at increased risk of cardiovascular events and mortality compared with non-PAD populations. Blood based biomarkers may improve clinical risk assessment. Recently, we found significant associations of serum glypican-4 (GPC4) with cardiovascular events and mortality in coronary angiography patients. The impact of serum GPC4 on the clinical outcome in PAD patients is unknown and has been addressed in a prospective cohort study. METHODS: We measured GPC4 levels using an enzyme-linked immunosorbent assay in 295 PAD patients. The primary endpoint was major adverse cardiovascular events (MACE); we further investigated vascular mortality and all-cause mortality over 10 years of follow-up. RESULTS: Serum GPC4 levels were positively linked with age, low kidney function, C-reactive protein (CRP), and the use of cardiovascular medications. During the 10-year follow-up period, MACE, vascular mortality, and all-cause mortality occurred in 43.1%, 33.4%, and 45.4%, respectively, of the patients. High serum GPC4 was significantly associated with all three endpoints (each log-rank P-value <0.001). In Cox regression analysis serum GPC4 significantly predicted MACE, vascular mortality, and all-cause mortality independently from traditional risk factors including age, sex, T2DM, hypertension, low kidney function, severity of PAD, smoking, and CRP, with adjusted hazard ratios [95% confidence interval] for one standard deviation change of serum GPC4 of 1.38 [1.06-1.80], 1.84 [1.28-2.64], and 1.94 [1.51-2.51], respectively. CONCLUSION: We conclude that serum GPC4 is a predictor of the 10-year clinical outcome in patients with PAD.

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines.

In vitro studies can help reveal the biochemical pathways underlying the origin of volatile indicators of numerous diseases. The key objective of this study is to identify the potential biomarkers of gastric cancer. For this purpose, the volatilomic signatures of two human gastric cancer cell lines, AGS (human gastric adenocarcinoma) and SNU-1 (human gastric carcinoma), and one normal gastric mucosa cell line (GES-1) were investigated. More specifically, gas chromatography mass spectrometry has been applied to pinpoint changes in cell metabolism triggered by cancer. In total, ten volatiles were found to be metabolized, and thirty-five were produced by cells under study. The volatiles consumed were mainly six aldehydes and two heterocyclics, whereas the volatiles released embraced twelve ketones, eight alcohols, six hydrocarbons, three esters, three ethers, and three aromatic compounds. The SNU-1 cell line was found to have significantly altered metabolism in comparison to normal GES-1 cells. This was manifested by the decreased production of alcohols and ketones and the upregulated emission of esters. The AGS cells exhibited the increased production of methyl ketones containing an odd number of carbons, namely 2-tridecanone, 2-pentadecanone, and 2-heptadecanone. This study provides evidence that the cancer state modifies the volatilome of human cells.

Evaluation of the association of serum glypican-4 with prevalent and future kidney function.

Serum glypican-4 (GPC4) has been identified as an insulin-sensitizing adipokine serving as a marker for body mass index and insulin resistance in humans. The association of circulating GPC4 with kidney function is to date largely unexplored. Therefore, we aimed to evaluate the association between serum GPC4 and prevalent as well future kidney function in a prospective cohort study. The study included 456 Caucasian coronary angiography patients. After a median follow up period of 3.4 years, data on kidney function was reassessed in all patients. Chronic kidney disease (CKD) was defined by decreased estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or albuminuria. At baseline, serum GPC4 was significantly associated with decreased eGFR (adjusted odds ratio (OR) per standard deviation = 4.75 [2.66-8.48]; P < 0.001), albuminuria (OR = 1.49 [1.15-1.92]; P = 0.002), and, accordingly, with CKD (OR = 1.75 [1.35-2.26]; P < 0.001). GPC4 levels also significantly and independently predicted the incidence of newly diagnosed decreased eGFR (OR = 2.74 [1.82-4.14]; P < 0.001, albuminuria (OR = 1.58 [1.01-2.46]; P = 0.043, and CKD (OR = 2.16 [1.45-3.23]; P < 0.001). ROC analysis indicated an additional predictive value of GPC4 to a basic prediction model for newly diagnosed CKD and eGFR < 60 mL/min/1.73 m2. Our study, therefore, indicates that high serum GPC4 is associated with decreased prevalent and future kidney function.

Data on the association of serum glypican-4 with future major adverse cardiovascular events and mortality in patients undergoing coronary angiography.

This data article is associated to the research article titled 'Serum glypican-4 is a marker of future vascular risk and mortality in coronary angiography patients' (Muendlein et al., 2022). The present article provides additional prospective data on the association of serum glypican-4 (GPC4) with the incidence of future major adverse cardiovascular events (MACE), vascular mortality, and overall mortality in a cohort of 760 coronary angiography patients. Serum GPC4 levels significantly differed between patients with or without an event during follow up. The results were confirmed in subgroup analyses with respect to age, sex, type 2 diabetes mellitus, obesity, the presence of significant coronary stenoses, and renal function, as well as medical treatment. That said, an interaction term between GPC4 and impaired renal function and between GPC4 and the use of beta blockers on the incidence of future fatal events reached statistical significance. In addition, C-statistics were performed showing an additional predictive value of categorized GPC4 to a basic risk model including traditional risk factors for overall mortality.

Serum glypican-4 is a marker of future vascular risk and mortality in coronary angiography patients.

BACKGROUND AND AIMS: Glypican-4 (GPC4) is a cell surface protein, but can be released into circulation under various clinical conditions. The association of circulating GPC4 with the risk of future cardiovascular events or death is unclear. In the present study, we aimed to investigate the association between serum GPC4 and major adverse cardiovascular events (MACE), vascular mortality, and all-cause mortality in a prospective cohort study. METHODS: Our study included 760 patients undergoing coronary angiography. During a mean follow up period of 6.3 years, the incidence of MACE, vascular mortality, and all-cause mortality was recorded. Serum GPC4 levels were determined using an enzyme-linked immunosorbent assay. RESULTS: Serum GPC4 was highly significantly associated with increased age, body mass index, brain natriuretic peptide, and oxidized low density lipoprotein, as well as with decreased estimated glomerular filtration rate. During the follow-up period, 145 patients died, including 67 vascular deaths. MACE occurred in 137 patients. Serum GPC4 was significantly associated with MACE, vascular mortality, and all-cause mortality independently of traditional cardiovascular risk factors, with adjusted hazard ratios (HR) and 95% confidence intervals for one standard deviation change of serum GPC4 of 1.32 [1.10-1.58], 1.38 [1.06-1.78], and 1.53 [1.29-1.82], respectively. The best cut-off value for serum GPC4 for predicting MACE, vascular mortality, and all-cause mortality was 7.24 ng/ml for all three endpoints. Respective adjusted HRs were 1.61 [1.07-2.43], 2.85 [1.62-5.01], and 2.92 [2.00-4.27]. CONCLUSIONS: Our study indicates that elevated serum GPC4 levels are significantly associated with an increased risk of MACE, vascular mortality, and all-cause mortality.

The LDL-C/ApoB ratio predicts major cardiovascular events in patients with established atherosclerotic cardiovascular disease.

BACKGROUND AND AIMS: The low density lipoprotein cholesterol to Apolipoprotein B (LDL-C/ApoB) ratio is a validated proxy for low density lipoprotein (LDL) particle size that can be easily calculated from a standard lipid/apolipoprotein profile. Whether it is predictive of cardiovascular events in patients with established atherosclerosis is not known and is addressed in the present investigation. METHODS: We determined the LDL-C/ApoB ratio in a cohort of 1687 subjects with established atherosclerosis. Prospectively, major cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a period of 9.9 ± 4.6 years. The study covers >16,000 patient-years. RESULTS: At baseline, the LDL-C/ApoB ratio was 1.36 ± 0.28 in our cohort. During follow up, a total of 558 first MACE were recorded. The LDL-C/ApoB ratio predicted MACE in univariate Cox proportional hazard analysis (HR 0.90 [0.82-0.98]; p = 0.014); this finding was confirmed after adjustment for age, gender, intensity of statin treatment, hypertension, history of smoking, type 2 diabetes, body mass index and ApoB (HR 0.87 [0.78-0.97]; p = 0.013). CONCLUSIONS: The LDL-C/ApoB ratio is independently predictive of MACE in subjects with established atherosclerosis.

Type 2 diabetes mellitus is a strong predictor of LDL cholesterol target achievement in patients with peripheral artery disease.

BACKGROUND AND AIMS: Patients with peripheral artery disease (PAD) are at a very high risk of cardiovascular events and strongly benefit from lowering LDL cholesterol (LDL-C); updated European Society of Cardiology guidelines recommend an LDL-C target of at least <55 mg/dl for these patients. Whether the presence of type 2 diabetes (T2DM) affects LDL-C target achievement in PAD patients is unknown and is addressed in the present study. METHODS: We investigated an unselected consecutive series of 319 patients with sonographically proven PAD, of whom 136 (42.6%) had T2DM. RESULTS: The LDL-C target of <55 mg/dl was met by 8.1% of T2DM patients and by 2.2% of non-diabetic patients (p = 0.014); LDL-C was <70 mg/dl in 22.8% of patients with T2DM and in 9.8% of non-diabetic patients (p = 0.002). Logistic regression analysis showed that the presence of T2DM was an independent and strong predictor of LDL-C target achievement after multivariate adjustment including age, gender, potency adjusted statin use, BMI, smoking, hypertension and other lipid-modifying therapy for the <55 mg/dl target (OR 3.58 [1.08-11.90]; p = 0.038) as well as for the <70 mg/dl target (OR 2.78 [1.40-5.35]; p = 0.003). CONCLUSION: We conclude that T2DM is a strong and independent predictor of LDL-C target achievement among PAD patients; however, also among PAD patients with T2DM only a minority meets the current target of <55 mg/dl and most patients do not even have an LDL-C < 70 mg/dl.

Usefulness of Handgrip Strength to Predict Mortality in Patients With Coronary Artery Disease.

Handgrip strength (HGS) is a validated and simple technique to estimate skeletal muscular strength. Whether HGS is a predictor of overall mortality in patients with established coronary artery disease (CAD) is not known, this question is therefore addressed in the present study. We prospectively investigated a cohort of 691 patients with angiographically proven CAD. HGS was measured at baseline, and all-cause death as well as cardiovascular events was recorded over a period of up to 12 years. During a follow-up time of 9.2 ± 3.1 years, 31.3% (n = 216) of the study participants died. Further, 27.8% (n = 192) suffered major cardiovascular events and 56.6% (n = 391) any cardiovascular event. Cox proportional hazard model analysis showed a reduced mortality risk with higher HGS univariately (hazard ratio [HR] for each 5 kg increase in HGS 0.87 [95% confidence interval 0.82 to 0.92]; p <0.001), after adjustment for age and gender (HR 0.86 [0.79 to 0.94]; p = 0.001), and after further adjustment for conventional cardiovascular risk factors (HR 0.86 [0.79 to 0.94]; p = 0.001). Similarly, high HGS was protective of major cardiovascular events as well as of total cardiovascular events (HRs in the fully adjusted model 0.86 [0.78 to 0.94]; p = 0.002 and 0.89 [0.83 to 0.96]; p = 0.002, respectively). From these data, we conclude that HGS is an independent predictor of overall survival and of cardiovascular events in patients with CAD.

Marked differences in prediabetes- and diabetes-associated comorbidities between men and women-Epidemiological results from a general population-based cohort aged 6-80 years-The LEAD (Lung, hEart, sociAl, boDy) study.

BACKGROUND: Based on biological and behavioural diversity sex and gender may affect comorbidities associated with prediabetes and diabetes. Besides evaluating the prevalence of prediabetes and diabetes (using fasting plasma glucose and HbA1c levels), the primary aim of the study is to investigate sex and gender differences in the prevalence of comorbidities in subjects with prediabetes and diabetes and to identify possible risk factors associated with prediabetes and diabetes. DESIGN: This observational, population-based cohort study included 11.014 subjects aged 6-80 years. Examinations included blood samples, ankle-brachial index, ECG, dual-energy X-ray absorptiometry scan and an interviewer-administered questionnaire. RESULTS: Across all ages, prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%), and 5.4% for diabetes (male 7.3%; female 3.7%). The prevalence of prediabetes ranged from 4.4% (6-<10 years) up to 40.4% (70+ years) in men and from 4.8% up to 42.3% in women. Comorbidity profile was markedly different between male and female, particularly in those with prediabetes: women more often suffered from arrhythmia, noncoronary artery disease, osteoporosis, increased systemic inflammatory biomarkers and depression, while men with prediabetes more often showed angina pectoris, myocardial infarction and media sclerosis. CONCLUSIONS: The unexpected 4.6% prevalence of prediabetes in children aged 6-10 underscores the need for population-based studies across all ages and the onset of prevention of diabetes at a young age. Marked differences have been found in comorbidities as men with prediabetes and diabetes more often suffer from cardiovascular disease, while women more often show arrhythmia, noncoronary artery disease, increased systemic inflammatory biomarkers and depression.

The Volatilomic Footprints of Human HGC-27 and CLS-145 Gastric Cancer Cell Lines.

The presence of certain volatile biomarkers in the breath of patients with gastric cancer has been reported by several studies; however, the origin of these compounds remains controversial. In vitro studies, involving gastric cancer cells may address this problem and aid in revealing the biochemical pathways underlying the production and metabolism of gastric cancer volatile indicators. Gas chromatography with mass spectrometric detection, coupled with headspace needle trap extraction as the pre-concentration technique, has been applied to map the volatilomic footprints of human HGC-27 and CLS-145 gastric cancer cell lines and normal Human Stomach Epithelial Cells (HSEC). In total, 27 volatile compounds are found to be associated with metabolism occurring in HGC-27, CLS-145, and HSEC. Amongst these, the headspace concentrations of 12 volatiles were found to be reduced compared to those above just the cultivating medium, namely there was an observed uptake of eight aldehydes (2-methylpropanal, 2-methyl-2-propenal, 2-methylbutanal, 3-methylbutanal, hexanal, heptanal, nonanal, and benzaldehyde), three heterocyclic compounds (2-methyl-furan, 2-ethyl-furan, and 2-pentyl-furan), and one sulfur-containing compound (dimethyl disulphide). For the other 15 volatiles, the headspace concentrations above the healthy and cancerous cells were found to be higher than those found above the cultivating medium, namely the cells were found to release three esters (ethyl acetate, ethyl propanoate, and ethyl 2-methylbutyrate), seven ketones (2-pentanone, 2-heptanone, 2-nonanone, 2-undecanone, 2-tridecanone, 2-pentadecanone, and 2-heptadecanone), three alcohols (2-methyl-1-butanol, 3-methyl-1-butanol, and 2-ethyl-1-hexanol), one aromatic compound (toluene), and one sulfur containing compound [2-methyl-5-(methylthio) furan]. In comparison to HSEC, HGC-27 cancer cell lines were found to have significantly altered metabolism, manifested by an increased production of methyl ketones containing an odd number of carbons. Amongst these species, three volatiles were found exclusively to be produced by this cell line, namely 2-undecanone, 2-tridecanone, and 2-heptadecanone. Another interesting feature of the HGC-27 footprint is the lowered level of alcohols and esters. The CLS-145 cells exhibited less pronounced changes in their volatilomic pattern compared to HSEC. Their footprint was characterized by the upregulated production of esters and 2-ethyl-hexanol and downregulated production of other alcohols. We have therefore demonstrated that it is possible to differentiate between cancerous and healthy gastric cells using biochemical volatile signatures.

Data on the impact of peripheral artery disease and of type 2 diabetes mellitus on the risk of cardiovascular events.

Here, we provide additional data addressing the individual and combined associations of type 2 diabetes (T2DM) and of peripheral artery disease (PAD) with future cardiovascular events in a prospective cohort study including 338 PAD patients and 711 patients who did not have PAD. Subgroup analyses regarding patient age as well as additional Cox regression models taking into account medications are presented. This data article is related to a research article titled "Single and combined effects of peripheral artery disease and of type 2 diabetes mellitus on the risk of cardiovascular events: a prospective cohort study" (Saely et al., 2018).

Single and combined effects of peripheral artery disease and of type 2 diabetes mellitus on the risk of cardiovascular events: A prospective cohort study.

BACKGROUND AND AIMS: The individual and combined effects of type 2 diabetes (T2DM) and peripheral artery disease (PAD) on future cardiovascular events are unknown and are addressed in the present investigation. METHODS: Cardiovascular events were prospectively recorded in 1049 subjects, encompassing 4 groups: 558 with neither PAD nor diabetes, 153 with T2DM but without PAD, 192 with PAD but without T2DM and 146 with the combination of PAD and T2DM. RESULTS: Over a mean follow-up period of 7.2 ±â€¯2.6 years, the cardiovascular event rate was lowest in patients with neither PAD nor T2DM (16.7%). Compared to this group the event rate was not significantly increased in T2DM patients without PAD (22.2%, p = 0.077) but higher in non-diabetic patients with PAD (52.6%; p < 0.001) and further increased in patients with both PAD and T2DM (71.2%; p < 0.001). Nondiabetic PAD patients were at a higher cardiovascular risk than T2DM patients without PAD (p < 0.001). Compared to those with neither PAD nor T2DM, hazard ratios after multivariate adjustment were 1.26 [0.84-1.91]; p = 0.267, 4.17 [2.97-5.85]; p < 0.001, and 7.82 [5.49-11.12]; p < 0.001 for those with T2DM only, for those with PAD only and for those with the combination of PAD plus diabetes, respectively. CONCLUSIONS: PAD is a stronger risk factor for future cardiovascular events than T2DM, but T2DM in PAD patients accelerates atherothrombotic disease and strongly increases the incidence of cardiovascular events.