Identification of Novel Diagnostic Biomarkers in Breast Cancer Using Targeted Metabolomic Profiling

Kozar, Nejc; Kruusmaa, Kristi; Bitenc, Marko; Argamasilla, Rosa; Adsuar, Antonio; Takač, Iztok; Arko, Darja

doi:10.1016/j.clbc.2020.09.006

Cited by 8 publications

(8 citation statements)

References 29 publications

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“…This transportation facilitates fatty acid beta-oxidation (FAO) within cells, playing a crucial role in energy metabolism to sustain cell activity [30]. Acyl-carnitines have been implicated in various disease states, including insulin resistance [31], obesity [32], breast cancer [33], hepatocellular carcinoma [34], and nonalcoholic fatty liver disease (NAFLD) [35,36]. In NAFLD patients, the serum levels of total acyl-carnitine increased gradually according to the progression of fibrosis, with even higher levels in hepatocellular carcinoma patients [36].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Plasma Lipid Profile before and after Surgical Removal of Soft Tissue Sarcoma

Lee,

Gwon,

Kim

et al. 2024

Metabolites

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Soft tissue sarcoma (STS) is a relatively rare malignancy, accounting for about 1% of all adult cancers. It is known to have more than 70 subtypes. Its rarity, coupled with its various subtypes, makes early diagnosis challenging. The current standard treatment for STS is surgical removal. To identify the prognosis and pathophysiology of STS, we conducted untargeted metabolic profiling on pre-operative and post-operative plasma samples from 24 STS patients who underwent surgical tumor removal. Profiling was conducted using ultra-high-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry. Thirty-nine putative metabolites, including phospholipids and acyl-carnitines were identified, indicating changes in lipid metabolism. Phospholipids exhibited an increase in the post-operative samples, while acyl-carnitines showed a decrease. Notably, the levels of pre-operative lysophosphatidylcholine (LPC) O-18:0 and LPC O-16:2 were significantly lower in patients who experienced recurrence after surgery compared to those who did not. Metabolic profiling may identify aggressive tumors that are susceptible to lipid synthase inhibitors. We believe that these findings could contribute to the elucidation of the pathophysiology of STS and the development of further metabolic studies in this rare malignancy.

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Section: Discussionmentioning

confidence: 99%

Alterations in Plasma Lipid Profile before and after Surgical Removal of Soft Tissue Sarcoma

Lee,

Gwon,

Kim

et al. 2024

Metabolites

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“…Classical diagnostic strategies, such as physical examination, mammography, and biopsy, are still limited for large-scale screening due to their inherent characteristics, calling for medical professionals with rich experience of years, large instruments of high cost in purchase/maintenance, or inevitable invasiveness with low population compliance ( 4 , 48 , 49 ). Previously, other MS techniques, including liquid chromatography-MS (LC-MS), gas chromatography-MS (GC-MS), and matrix-assisted laser desorption ionization-MS, have been explored in previous studies for BrCa diagnosis ( 12 , 47 , 50 – 52 ). Compared with those studies ( SI Appendix , Table S12 ), our work was conducted based on a well-designed cohort and showed desirable diagnostic performance with an AUC of 0.948 (95% CI of 0.922 to 0.973), which is promising for large-scale screening use in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and prognosis of breast cancer by high-performance serum metabolic fingerprints

Huang

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Breast cancer (BrCa) is the most common cancer worldwide, and high-performance metabolic analysis is emerging in diagnosis and prognosis of BrCa. Here, we used nanoparticle-enhanced laser desorption/ionization mass spectrometry to record serum metabolic fingerprints of BrCa in seconds, achieving high reproducibility and low consumption of direct serum detection. Our analytical method, combined with the aid of machine learning algorithms, was demonstrated to provide high diagnostic efficiency with accuracy of 88.8% and desirable prognostic prediction ( P < 0.005). Furthermore, seven metabolic biomarkers differentially enriched in BrCa serum and their related pathways were identified. Together, our findings provide a tool to characterize BrCa and highlight certain metabolic signatures as potential diagnostic and prognostic factors of diseases including but not limited to BrCa.

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“…Molecular imaging techniques enable the detection of cellular and molecular abnormalities during tumor progression. − Therefore, in situ imaging of tumor cells based on intracellular tumor biomarkers at the molecular level is urgently needed. Amplification-based molecular imaging strategies, such as the catalytic hairpin assembly (CHA) reaction-based approach and the enzymatically amplified-based approach, are extensively employed in tumor molecular imaging due to the relatively low expression levels of tumor biomarkers. − However, the majority of biomarkers, including RNA, glycoproteins, and ions can also be present in normal cells at significant levels. ,,− These biomarkers can be detected using amplification-based techniques, resulting in low signal-to-background ratios and posing a considerable challenge for tumor-specific molecular sensing. Therefore, the development of spatially specific molecular imaging approaches is imperative.…”

Section: Introductionmentioning

confidence: 99%

An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging

Zhang,

Zhang

et al. 2024

Anal. Chem.

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Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1 AP , and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1 AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1 AP ). Subsequently, miRNA-21 facilitates the hybridization of activated H1 AP on tFNA-H1 AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1 AP at the vertices of tFNA-H1 AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The ANDgated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.

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Identification of Novel Diagnostic Biomarkers in Breast Cancer Using Targeted Metabolomic Profiling

Cited by 8 publications

References 29 publications

Alterations in Plasma Lipid Profile before and after Surgical Removal of Soft Tissue Sarcoma

Alterations in Plasma Lipid Profile before and after Surgical Removal of Soft Tissue Sarcoma

Diagnosis and prognosis of breast cancer by high-performance serum metabolic fingerprints

An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging

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