Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC). Sector-22, Kharghar, Navi Mumbai 410210, India.
Anal Chem. 2022 Aug 30;94(34):11898-11907. doi: 10.1021/acs.analchem.2c02487. Epub 2022 Aug 18.
To date, no studies are available in which pituitary adenomas (PAs) have been studied using techniques like confocal Raman spectroscopy, attenuated total reflection-Fourier transform infrared (FT-IR), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the same serum samples. To understand the metabolomics fingerprint, Raman spectra of 16 acromegaly, 19 Cushing's, and 33 nonfunctional PA (NFPA) and ATR-FTIR spectral acquisition of 16 acromegaly, 18 Cushing's, and 22 NFPA patient's serum samples were acquired. Next, Principal component-based linear discriminant analysis (PC-LDA) models were developed, Raman spectral analysis classified acromegaly with an accuracy of 79.17%, sensitivity of 75%, and specificity of 81.25%, Cushing's with an accuracy of 66.67%, sensitivity of 100%, and specificity of 52.63%, and NFPA with an accuracy of 73.17%, sensitivity of 75%, and specificity of 72.73%. ATR-FTIR spectral analysis classified acromegaly with an accuracy of 95.83%, sensitivity of 100%, and specificity of 93.75%, Cushing's with an accuracy of 65.38%, sensitivity of 87.5%, and specificity of 55.56%, and NFPA with an accuracy of 70%, sensitivity of 87.5%, and specificity of 43.75%. In either of the cases, healthy individual cohorts were clearly segregated from the disease cohort, which identified differential regulated regions of nucleic acids, lipids, amides, phosphates, and polysaccharide/C-C residue α helix regions. Furthermore, LC-MS/MS-based analysis of sera samples resulted in the identification of various sphingosine, lipids, acylcarnitines, amino acids, ethanolamine, choline, and their derivatives that differentially regulated in each tumor cohort. We believe cues obtained from the study may be used to generate the metabolite-based test to diagnose PAs from serum in addition to conventional techniques and also to understand disease biology for better disease management, point of care, and improving quality of life in PA patients.
迄今为止，尚无研究在同一血清样本中使用共焦拉曼光谱、衰减全反射傅里叶变换红外（FT-IR）和液相色谱-串联质谱（LC-MS/MS）等技术对垂体腺瘤（PA）进行研究。为了了解代谢组学指纹图谱，我们获取了 16 例肢端肥大症、19 例库欣病和 33 例无功能 PA（NFPA）的拉曼光谱，以及 16 例肢端肥大症、18 例库欣病和 22 例 NFPA 患者血清样本的衰减全反射傅里叶变换红外光谱。然后，建立了基于主成分的线性判别分析（PC-LDA）模型，拉曼光谱分析对肢端肥大症的准确率为 79.17%，灵敏度为 75%，特异性为 81.25%，对库欣病的准确率为 66.67%，灵敏度为 100%，特异性为 52.63%，对 NFPA 的准确率为 73.17%，灵敏度为 75%，特异性为 72.73%。衰减全反射傅里叶变换红外光谱分析对肢端肥大症的准确率为 95.83%，灵敏度为 100%，特异性为 93.75%，对库欣病的准确率为 65.38%，灵敏度为 87.5%，特异性为 55.56%，对 NFPA 的准确率为 70%，灵敏度为 87.5%，特异性为 43.75%。在这两种情况下，健康个体队列都与疾病队列明显分开，这确定了核酸、脂质、酰胺、磷酸盐和多糖/C-C 残基α螺旋区域的差异调节区域。此外，基于 LC-MS/MS 的血清样本分析结果鉴定了不同肿瘤队列中差异调节的各种神经鞘氨醇、脂质、酰基肉碱、氨基酸、乙醇胺、胆碱及其衍生物。我们相信，从这项研究中获得的线索可能用于在常规技术之外，从血清中生成基于代谢物的 PA 诊断测试，还可以了解疾病生物学，从而更好地进行疾病管理、即时护理，并提高 PA 患者的生活质量。
