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  • The salivary volatome in breast cancer
    Publication . Pereira, Jorge A. M.; Taware, Ravindra; Porto-Figueira, Priscilla; Rapole, Srikanth; Câmara, José S.
  • Extracellular volatilomic alterations induced by hypoxia in breast cancer cells
    Publication . Taware, Ravindra; Taunk, Khushman; Kumar, Totakura V. S.; Pereira, Jorge A. M.; Câmara, José S.; Nagarajaram, H. A.; Kundu, Gopal C.; Rapole, Srikanth
    Introduction The metabolic shift induced by hypoxia in cancer cells has not been explored at volatilomic level so far. The volatile organic metabolites (VOMs) constitute an important part of the metabolome and their investigation could provide us crucial aspects of hypoxia driven metabolic reconfguration in cancer cells. Objective To identify the altered volatilomic response induced by hypoxia in metastatic/aggressive breast cancer (BC) cells. Methods BC cells were cultured under normoxic and hypoxic conditions and VOMs were extracted using HS-SPME approach and profled by standard GC–MS system. Univariate and multivariate statistical approaches (p<0.05, Log2 FC≥0.58/≤−0.58, PC1>0.13/<−0.13) were applied to select the VOMs diferentially altered after hypoxic treatment. Metabolic pathway analysis was also carried out in order to identify altered metabolic pathways induced by the hypoxia in the selected BC cells. Results Overall, 20 VOMs were found to be signifcantly altered (p<0.05, PC1>0.13/< −0.13) upon hypoxic exposure to BC cells. Further, cell line specifc volatilomic alterations were extracted by comparative metabolic analysis of aggressive (MDA-MB-231) vs. non-aggressive (MCF-7) cells incubated under hypoxia and normoxia. In this case, 15 and 12 VOMs each were found to be signifcantly altered in aggressive cells when exposed to hypoxic and normoxic condition respectively. Out of these, 9 VOMs were found to be uniquely associated with hypoxia, 6 were specifc to normoxia and 6 were found common to both the conditions. Formic acid was identifed as the most prominent molecule with higher abundance levels in aggressive as compared to non-aggressive cells in both conditions. Furthermore, metabolic pathway analyses revealed that fatty acid biosynthesis and nicotinate and nicotinamide metabolism were signifcantly altered in aggressive as compared to non-aggressive cells in normoxia and hypoxia respectively. Conclusions Higher formate overfow was observed in aggressive cells compared to non-aggressive cells incubated under both the conditions, reinforcing its correlation with aggressive and invasive cancer type. Moreover, under hypoxia, aggres sive cells preferred to be bioenergetically more efcient whereas, under normoxia, fatty acid biosynthesis was favoured when compared to non-aggressive cells.
  • Urinary Volatomic Expression Pattern: Paving the Way for Identification of Potential Candidate Biosignatures for Lung Cancer
    Publication . Taunk, Khushman; Porto-Figueira, Priscilla; Pereira, Jorge A. M.; Taware, Ravindra; Costa, Nattane Luíza da; Barbosa, Rommel; Rapole, Srikanth; Câmara, José S.
    The urinary volatomic profiling of Indian cohorts composed of 28 lung cancer (LC) pa tients and 27 healthy subjects (control group, CTRL) was established using headspace solid phase microextraction technique combined with gas chromatography mass spectrometry methodology as a powerful approach to identify urinary volatile organic metabolites (uVOMs) to discriminate among LC patients from CTRL. Overall, 147 VOMs of several chemistries were identified in the intervention groups—including naphthalene derivatives, phenols, and organosulphurs—augmented in the LC group. In contrast, benzene and terpenic derivatives were found to be more prevalent in the CTRL group. The volatomic data obtained were processed using advanced statistical analysis, namely partial least square discriminative analysis (PLS-DA), support vector machine (SVM), random forest (RF), and multilayer perceptron (MLP) methods. This resulted in the identification of nine uVOMs with a higher potential to discriminate LC patients from CTRL subjects. These were furan, o-cymene, furfural, linalool oxide, viridiflorene, 2-bromo-phenol, tricyclazole, 4-methyl-phenol, and 1-(4-hydroxy-3,5-di-tert-butylphenyl)-2-methyl-3-morpholinopropan-1-one. The metabolic pathway analysis of the data obtained identified several altered biochemical pathways in LC mainly affecting glycolysis/gluconeogenesis, pyruvate metabolism, and fatty acid biosynthesis. Moreover, acetate and octanoic, decanoic, and dodecanoic fatty acids were identified as the key metabolites responsible for such deregulation. Furthermore, studies involving larger cohorts of LC patients would allow us to consolidate the data obtained and challenge the potential of the uVOMs as candidate biomarkers for LC.
  • Unravelling the potential of salivary volatile metabolites in oral diseases. A review
    Publication . Pereira, Jorge A. M.; Porto-Figueira, Priscilla; Taware, Ravindra; Sukul, Pritam; Rapole, Srikanth; Câmara, José S.
    Fostered by the advances in the instrumental and analytical fields, in recent years the analysis of volatile organic compounds (VOCs) has emerged as a new frontier in medical diagnostics. VOCs analysis is a non-invasive, rapid and inexpensive strategy with promising potential in clinical diagnostic procedures. Since cellular metabolism is altered by diseases, the resulting metabolic effects on VOCs may serve as biomarkers for any given pathophysiologic condition. Human VOCs are released from biomatrices such as saliva, urine, skin emanations and exhaled breath and are derived from many metabolic pathways. In this review, the potential of VOCs present in saliva will be explored as a monitoring tool for several oral diseases, including gingivitis and periodontal disease, dental caries, and oral cancer. Moreover, the analytical state-of-the-art for salivary volatomics, e.g., the most common extraction techniques along with the current challenges and future perspectives will be addressed unequivocally