Mishra Abhay, Zehra Sadaqa, Bharti Prahalad Kumar, Mathur Sandeep R, Ranjan Piyush, Batra Atul, Inampudi Krishna K, Modi Gyan Prakash, Nikolajeff Fredrik, Kumar Saroj
Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India.
Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Sci Rep. 2024 Apr 23;14(1):9347. doi: 10.1038/s41598-024-59863-1.
Breast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C-H stretching of CH3. The study focused on the lipid region (3050-2900 cm), identifying peaks (3015 cm, 2960 cm, 2929 cm) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios [(I3015/I2929), (I2960/I2929)] emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C-H stretching vibrations, and C-O stretching at 1033 cm. Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection.
乳腺癌是女性死亡的主要原因之一，因其无症状特性和早期诊断工具有限导致检测延迟。本研究采用多模态方法对乳腺癌进行了调查。分析了乳腺癌患者（BrCa，n = 74）和健康对照者（HC，n = 30）血浆来源的小细胞外囊泡。通过化学沉淀分离出的小细胞外囊泡（n = 104），采用透射电子显微镜（TEM）和纳米颗粒跟踪分析（NTA）进行表征。验证涉及基于抗体的检测（TSG101、CD9、CD81、CD63）。获得了小细胞外囊泡的红外光谱，揭示了脂质酰基链的显著差异，特别是CH3的C-H伸缩振动。该研究聚焦于脂质区域（3050 - 2900 cm），将峰（3015 cm、2960 cm、2929 cm）确定为独特的脂质特征。光谱脂质比[（I3015/I2929）、（I2960/I2929）]成为突出的乳腺癌标志物。对蛋白质、核酸和碳水化合物比例的探索表明，α螺旋、不对称C-H伸缩振动和1033 cm处的C-O伸缩存在差异。主成分分析（PCA）成功区分了BrCa和HC小细胞外囊泡，热图分析和受试者工作特征（ROC）曲线评估强调了脂质比的鉴别能力。值得注意的是，（I2960/I2929）表现出100%的敏感性和特异性，突出了其作为乳腺癌检测中强大的BrCa小细胞外囊泡标志物物的潜力。
