Alteration in lipid composition differentiates breast cancer tissues: a 1H HRMAS NMR metabolomic study
Breast cancer is the most frequent diagnosed cancer among women with a mortality rate of 15% of all cancer related deaths in women. Breast cancer is heterogeneous in nature and produces plethora of metabolites allowing its early detection using molecular diagnostic techniques like magnetic resonance spectroscopy.
To evaluate the variation in metabolic profile of breast cancer focusing on lipids as triglycerides (TG) and free fatty acids (FFA) that may alter in malignant breast tissues and lymph nodes from adjacent benign breast tissues by HRMAS 1H NMR spectroscopy.
The 1H NMR spectra recorded on 173 tissue specimens comprising of breast tumor tissues, adjacent tissues, few lymph nodes and overlying skin tissues obtained from 67 patients suffering from breast cancer. Multivariate statistical analysis was employed to identify metabolites acting as major confounders for differentiation of malignancy.
Reduction in lipid content were observed in malignant breast tissues along with a higher fraction of FFA. Four small molecule metabolites e.g., choline containing compounds (Chocc), taurine, glycine, and glutamate were also identified as major confounders. The test set for prediction provided sensitivity and specificity of more than 90% excluding the lymph nodes and skin tissues.
Fatty acids composition in breast cancer using in vivo magnetic resonance spectroscopy (MRS) is gaining its importance in clinical settings (Coum et al. in Magn Reson Mater Phys Biol Med 29:1–4, 2016). The present study may help in future for precise evaluation of lipid classification including small molecules as a source of early diagnosis of invasive ductal carcinoma by employing in vivo magnetic resonance spectroscopic methods.
KeywordsBreast cancer Malignant tumor tissue Benign tissue HRMAS 1H NMR spectroscopy Triglycerides PUFA MUFA SFA Metabolic profiling
High resolution magic angle spinning
Nuclear overhauser effect spectroscopy
Nuclear magnetic resonance
Principal component analysis
Orthogonal signal correction
Orthogonal partial least square discriminant analysis
Variable importance in projection
QUANTification by Artificial Signal
The authors are thankful to Division of SAIF, CSIR-Centre of Drug Research Institute, Lucknow where the HRMAS 1H NMR measurements were conducted. Mr. Anup Paul would like to extend his thanks to UGC (SRF Award No. 18-12/2011(ii)EU-V) for financial assistance.
SK, AAS and RR designed the study. SK, AAS and AR performed the surgery and sampled the tissue specimens. AR, SK, RR and AP has conducted the experiments. AP, SK and RR analyzed the data. AS performed the histopathology. Initial draft written by AP. SK, AS and RR edited and revised the paper. Project administration of the study have carried under SK, AAS, SJ and RR. All authors carefully read and agree to be accountable for all aspects of the work.
Compliance with ethical standards
Conflict of interest
The authors have no potential conflict of interest. The disclosure of potential conflict of interest in the prescribed format has been obtained from all the authors.
The study was ethically approved and the work was performed in strict accordance with the guidelines of Institutional Ethical Committee of King George’s Medical University (KGMU) (Ref. Code: XXII ECM/P 6). The subjects were explained the study procedure and written and informed consent were obtained from them prior to the study. The authors: Anup Paul, Surendra Kumar, Anubhav Raj, Abhinav Sonkar, Sudha Jain, Atin Singhai and Raja Roy are aware of ethical policy.
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