UPLC-QTOF-MS-Based Plasma Lipidomic Profiling Reveals Biomarkers for Inflammatory Bowel Disease Diagnosis.
基于 UPLC-QTOF-MS 的血浆脂质组学分析揭示了炎症性肠病诊断的生物标志物。
- 作者列表："Guan S","Jia B","Chao K","Zhu X","Tang J","Li M","Wu L","Xing L","Liu K","Zhang L","Wang X","Gao X","Huang M
:Identification of new biomarkers may help in the early diagnosis of inflammatory bowel disease (IBD). In this study, ultrahigh-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to analyze the untargeted lipidomics and compare plasma lipid profiles between IBD patients and control subjects. The principal component analysis and partial least-squares-discriminant analysis were carried out to distinguish IBD patients from control subjects. Using univariate and multivariate analysis, 55 significantly different metabolites from five lipid classes, fatty acyls (n = 19), glycerophospholipids (n = 5), prenol lipids (n = 10), sphingolipids (n = 2), and sterol lipids (n = 19) were identified. Forty-four of the 55 metabolites were analyzed by receiver operating characteristic (ROC) curve and area under curve (AUC) of >0.80. After validation in an independent cohort, IBD patients were differentiated from the control subjects by significantly altered plasma level of palmitic acid, 7alpha, 25-dihydroxycholesterol, 20-hydroxyeicosatetraenoic (HETE)-d6, (+/-)5,6-epoxy-eicosatrienoic acid (EpETrE), docosahexaenoic acid (DHA), 9-heptadecylenic acid, lactucaxanthin, α-carotene, traumatic acid, and neoquassin with both sensitivity and specificity above 80%. Pathway analysis suggested that IBD dysregulation was related to the biosynthesis of primary bile acid, the metabolism of arachidonic acid, the metabolism of sphingolipid, fatty acid elongation, and glycerophospholipid metabolism. Our results suggest that the lipidomic profiling of patients plasma could be a potential method for IBD diagnosis.
: 新的生物标志物的鉴定可能有助于炎症性肠病 (IBD) 的早期诊断。在本研究中，超高效液相色谱配有四极杆飞行时间质谱 (UPLC-QTOF-MS) 用于分析非靶向脂质组学，比较 IBD 患者和对照组受试者的血脂谱。采用主成分分析和偏最小二乘判别分析区分 IBD 患者和对照组。使用单变量和多变量分析，来自五种脂质类别的 55 种显著不同的代谢物，脂肪酰基 (n = 19)，甘油磷脂 (n = 5)，戊烯醇脂质 (n = 10), 鉴定了鞘脂类 (n = 2) 和固醇脂类 (n = 19)。55 种代谢物中的 44 种通过受试者工作特征 (ROC) 曲线和> 0.80 的曲线下面积 (AUC) 进行分析。在独立队列中验证后，通过显著改变棕榈酸、 7 α，25-二羟基胆固醇、 20-羟基二十碳四烯酸 (HETE)-d6 的血浆水平将 IBD 患者与对照组受试者区分。 (+/-) 5，6-环氧二十碳三烯酸 (epete)，二十二碳六烯酸 (DHA)，9-十七碳烯酸，内酯黄质，α-胡萝卜素，外伤酸,和 neoquassin，敏感性和特异性均在 80% 以上。通路分析表明，IBD 失调与初级胆汁酸的生物合成、花生四烯酸的代谢、鞘脂的代谢、脂肪酸的延伸和甘油磷脂的代谢有关。我们的结果表明，患者血浆的脂质组学分析可能是 IBD 诊断的潜在方法。
METHODS:Purpose Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs). Methods We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015. Clinical data were extracted from electronic medical records. MRI texture analysis was performed on preoperative non-enhanced T1-weighted images using ImageJ (NIH). Logistic and Cox models were used to determine if image texture parameters predicted outcomes. Results Eighty-nine patients had texture parameters measured, which were compared to that of NFPAs, while 64 of these patients had follow-up and were included in the remainder of analyses. Minimum pixel intensity, skewness, and kurtosis were significantly different in somatotroph adenomas versus NFPAs (area under the receiver operating characteristic curve, 0.7771, for kurtosis). Furthermore, those with a maximum pixel intensity above the median had an increased odds of IGF-I normalization on SRL therapy (OR 5.96, 95% CI 1.33–26.66), which persisted after adjusting for several potential predictors of response. Image texture did not predict tumor recurrence or progression. Conclusion Our data suggest that MRI texture analysis can distinguish NFPAs from somatotroph macroadenomas with good diagnostic accuracy and can predict normalization of IGF-I with SRL therapy.
METHODS::Growth hormone-secreting pituitary adenoma (GHPA), a benign endocrine tumor located in the base of the skull, results in acromegaly. In addition to the mass effect of the tumor itself in the sellar region, GHPA can lead to the overgrowth of almost every organ. Previous findings indicated that the processes underlying acromegaly were partly attributable to hyperactivity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. However, the mechanisms driving this syndrome remains largely unknown. Additionally, the roles of GHPA-derived exosomes, which contain functional microRNAs and proteins that manipulate target cell proliferation and differentiation in distal extremities, are also unknown. In this study, we demonstrated that GHPA exosomes promote bone formation in vitro and trabecula number in vivo. The mechanism of increased trabecula formation may be attributable to GHPA exosome-induced osteoblast proliferation via increased cell viability and DNA replication. We further discovered that exosomal hsa-miR-21-5p plays a distinct role from the GH/IGF-1 axis in these processes. Accordingly, the results of this study provide a novel mechanism whereby GHPA influences distal extremities and a new perspective for treating GHPA.
METHODS:BACKGROUND:Fibroblast growth factor 21 (FGF21) is a circulating hormone with pleiotropic metabolic effects, which is inactivated by fibroblast activation protein (FAP). Data regarding interaction between FGF21, FAP, and growth hormone (GH) are limited, but it is noteworthy that collagens are also FAP substrates, since GH potently stimulates collagen turnover. AIM:To measure circulating FGF21 components, including FAP, in patients with acromegaly before and after disease control. METHODS:Eighteen patients with active acromegaly were studied at the time of diagnosis and ≥ 6 months after disease control by either surgery or medical treatment. Serum levels of total and active FGF21, β-klotho, FAP, and collagen turnover markers were measured by immunoassays. Expression of putative FGF21-dependent genes were measured in adipose tissue by reverse transcriptase-polymerase chain reaction, body composition assessed by dual-energy x-ray absorptiometry scan, and insulin sensitivity estimated with homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS:Total FGF21, active FGF21 and β-klotho remained unchanged. Insulin sensitivity and body fat mass increased after disease control but neither correlated with active FGF21. Expression of FGF21-dependent genes did not change after treatment. FAP levels (µg/L) were markedly reduced after treatment [105.6 ± 29.4 vs 62.2 ± 32.4, P < 0.000]. Collagen turnover markers also declined significantly after treatment and ΔFAP correlated positively with ΔProcollagen Type I (P < 0.000) and Type III (P < 0.000). CONCLUSION:1) Circulating FGF21 and β-klotho do not change in response to acromegaly treatment, 2) FAP concentrations in serum decrease after disease control and correlate positively with collagen turnover markers, and 3) FAP is a hitherto unrecognized GH target linked to collagen turnover. CLINICAL TRIALS REGISTRATION:NCT00647179.