Taware Ravindra, More Tushar H, Bagadi Muralidhararao, Taunk Khushman, Mane Anupama, Rapole Srikanth
Proteomics Lab, National Centre for Cell Science Ganeshkhind Pune-411007 MH India
Grant Medical Foundation, Ruby Hall Clinic Pune-411001 MH India.
RSC Adv. 2020 Dec 22;11(1):397-407. doi: 10.1039/d0ra07368g. eCollection 2020 Dec 21.
The need of identifying alternative therapeutic targets for invasive ductal carcinoma (IDC) of the breast with high specificity and sensitivity for effective therapeutic intervention is crucial for lowering the risk of fatality. Lipidomics has emerged as a key area for the discovery of potential candidates owing to its several shared pathways between cancer cell proliferation and survival. In the current study, we performed comparative phospholipidomic analysis of IDC, benign and control tissue samples of the breast to identify the significant lipid alterations associated with malignant transformation. A total of 33 each age-matched tissue samples from malignant, benign and control were analyzed to identify the altered phospholipids by using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM/MS). A combination of univariate and multivariate statistical approaches was used to select the phospholipid species with the highest contribution in group segregation. Furthermore, these altered phospholipids were structurally confirmed by tandem mass spectrometry. A total of 244 phospholipids were detected consistently at quantifiable levels, out of which 32 were significantly altered in IDC of the breast. Moreover, in pairwise comparison of IDC against benign and control samples, 11 phospholipids were found to be significantly differentially expressed. Particularly, LPI 20:3, PE (22:1/22:2), LPE 20:0 and PC (20:4/22:4) were observed to be most significantly associated with IDC tissue samples. Apart from that, we also identified that long-chain unsaturated fatty acids were enriched in the IDC tissue samples as compared to benign and control samples, indicating its possible association with the invasive phenotype.
对于侵袭性导管癌(IDC)而言,确定具有高特异性和敏感性的替代治疗靶点以进行有效的治疗干预,对于降低死亡风险至关重要。脂质组学由于在癌细胞增殖和存活之间存在多个共享途径,已成为发现潜在候选物的关键领域。在本研究中,我们对乳腺癌的IDC、良性和对照组织样本进行了比较磷脂组学分析,以确定与恶性转化相关的显著脂质变化。通过液相色谱 - 多反应监测质谱法(LC - MRM/MS)分析了来自恶性、良性和对照的各33个年龄匹配的组织样本,以鉴定改变的磷脂。使用单变量和多变量统计方法相结合来选择在组间分离中贡献最大的磷脂种类。此外,通过串联质谱对这些改变的磷脂进行了结构确认。共一致检测到244种可定量水平的磷脂,其中32种在乳腺癌的IDC中显著改变。此外,在IDC与良性和对照样本的成对比较中,发现11种磷脂有显著差异表达。特别地,观察到LPI 20:3、PE(22:1/22:2)、LPE 20:0和PC(20:4/22:4)与IDC组织样本最显著相关。除此之外,我们还发现与良性和对照样本相比,长链不饱和脂肪酸在IDC组织样本中富集,表明其可能与侵袭性表型相关。