An Innovative Platform Merging Elemental Analysis and Ftir Imaging for Breast Tissue Analysis

Ali, Maha; Rakib, Fazle; Al‐Saad, Khalid; Al-Saady, Rafif; Goormaghtigh, Erik

doi:10.1038/s41598-019-46056-4

Cited by 20 publications

(26 citation statements)

References 61 publications

(74 reference statements)

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“…We have also previously utilized FTIR spectroscopy as a bio-diagnostics tool for investigation of rat brain after ischemic stroke [46], characterization of different brain regions [33], and improving tissue classification [42]. We have also demonstrated the use of FTIR bio-spectroscopy, combined with another elemental analysis approach, to examine breast tissues in order to provide a single set of markers based on both organic molecules and inorganic trace elements [63]. Herein, for the first time, this study has explored the biochemical and molecular changes in breast cancer cells after atezolizumab treatment.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy

et al. 2019

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Interactions between programmed death-1 (PD-1) with its ligand PD-L1 on tumor cells can antagonize T cell responses. Inhibiting these interactions using immune checkpoint inhibitors has shown promise in cancer immunotherapy. MDA-MB-231 is a triple negative breast cancer cell line that expresses PD-L1. In this study, we investigated the biochemical changes in MDA-MB-231 cells following treatment with atezolizumab, a specific PD-L1 blocker. Our readouts were Fourier Transform Infrared (FTIR) spectroscopy and flow cytometric analyses. Chemometrical analysis, such as principal component analysis (PCA), was applied to delineate the spectral differences. We were able to identify the chemical alterations in both protein and lipid structure of the treated cells. We found that there was a shift from random coil and α-helical structure to β-sheet conformation of PD-L1 on tumor cells due to atezolizumab treatment, which could hinder binding with its receptors on immune cells, ensuring sustained T cell activation for potent immune responses. This work provides novel information about the effects of atezolizumab at molecular and cellular levels. FTIR bio-spectroscopy, in combination with chemometric analyses, may expedite research and offer new approaches for cancer immunology.

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Section: Discussionmentioning

confidence: 99%

Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy

et al. 2019

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“…Fourier Transform Infrared (FTIR) imaging spectroscopy is able to screen changes within of biological samples on a molecular level [5,20,21]. By means of FTIR imaging, one should be able to observe molecular changes of brain tissues and their spatial distribution [5,22].…”

Section: Introductionmentioning

confidence: 99%

“…The elegance of this technique is that it needs almost no sample preparation other than sectioning as per normal tissue techniques, leaving the sample unchanged after collection of the IR spectra. This assures reproducible measurements and makes FTIR convenient for combining with other standard staining techniques and other molecular probes [5,20,23]. FTIR imaging has the ability to detect, simultaneously, discrete changes in molecular structure and composition of tissues, which cannot be done by standard histological staining methods.…”

Section: Introductionmentioning

confidence: 99%

“…Ali et al also showed the sensitivity and high resolution of FTIR spectroscopy in characterizing different brain tissue regions [23]. By choosing optimal biomarkers, FTIR not only discriminates diseased from healthy tissue but it also is capable of grading stages of malignancy, which is very important for determining treatment methods [20,36,37]. Richter et al have combined FTIR measurements with positron emitting tomography (PET) in order to identify tumor tissues [38].…”

Section: Introductionmentioning

confidence: 99%

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Investigation of Biochemical Alterations in Ischemic Stroke Using Fourier Transform Infrared Imaging Spectroscopy—A Preliminary Study

et al. 2019

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Objective: Brain damage, long-term disability and death are the dreadful consequences of ischemic stroke. It causes imbalance in the biochemical constituents that distorts the brain dynamics. Understanding the sub-cellular alterations associated with the stroke will contribute to deeper molecular understanding of brain plasticity and recovery. Current routine approaches examining lipid and protein biochemical changes post stoke can be difficult. Fourier Transform Infrared (FTIR) imaging spectroscopy can play a vital role in detecting these molecular alterations on a sub-cellular level due to its high spatial resolution, accuracy and sensitivity. This study investigates the biochemical and molecular changes in peri-infract zone (PIZ) (contiguous area not completely damaged by stroke) and ipsi-lesional white matter (WM) (right below the stroke and PIZ regions) nine weeks post photothrombotic ischemic stroke in rats. Materials and Methods: FTIR imaging spectroscopy and transmission electron microscopy (TEM) techniques were applied to investigate brain tissue samples while hematoxylin and eosin (H&E) stained images of adjacent sections were prepared for comparison and examination the morphological changes post stroke. Results: TEM results revealed shearing of myelin sheaths and loss of cell membrane, structure and integrity after ischemic stroke. FTIR results showed that ipsi-lesional PIZ and WM experienced reduction in total protein and total lipid content compared to contra-lesional hemisphere. The lipid/protein ratio reduced in PIZ and adjacent WM indicated lipid peroxidation, which results in lipid chain fragmentation and an increase in olefinic content. Protein structural change is observed in PIZ due to the shift from random coli and α-helical structures to β-sheet conformation. Conclusion: FTIR imaging bio-spectroscopy provide novel biochemical information at sub-cellular levels that be difficult to be obtained by routine approaches. The results suggest that successful therapeutic strategy that is based on administration of anti-oxidant therapy, which could reduce and prevent neurotoxicity by scavenging the lipid peroxidation products. This approach will mitigate tissue damage in chronic ischemic period. FTIR imaging bio-spectroscopy can be used as a powerful tool and offer new approach in stroke and neurodegenerative diseases research.

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“…Instead of analyzing every pixel in the tissue without the context of tumor architecture, we first focused on determining the histologic identity of each pixel. This pixel-level identification is accomplished by applying machine learning to the acquired spectral data, as well described by numerous works for breast tissue [16][17][18][19][20][21][22][23][24][25][26][27] . Here, we first segmented the tissue image into histological components by applying a previously described histological classifier that labeled each pixel in the tissue section as one of the tissue classes i.e.…”

Section: Classification Of Ecm3 and Non-ecm3 Tumors By Ft-ir Previoumentioning

confidence: 99%

Infrared Spectroscopic Imaging Visualizes a Prognostic Extracellular Matrix-Related Signature in Breast Cancer

Tiwari

Triulzi

Holton

et al. 2020

Sci Rep

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Molecular analysis techniques such as gene expression analysis and proteomics have contributed greatly to our understanding of cancer heterogeneity. In prior studies, gene expression analysis was shown to stratify patient outcome on the basis of tumor-microenvironment associated genes. A specific gene expression profile, referred to as ECM3 (Extracellular Matrix Cluster 3), indicated poorer survival in patients with grade III tumors. In this work, we aimed to visualize the downstream effects of this gene expression profile onto the tissue, thus providing a spatial context to altered gene expression profiles. Using infrared spectroscopic imaging, we identified spectral patterns specific to the ECM3 gene expression profile, achieving a high spectral classification performance of 0.87 as measured by the area under the curve of the receiver operating characteristic curve. On a patient level, we correctly identified 20 out of 22 ECM3 group patients and 19 out of 20 non-ECM3 group patients by using this spectroscopic imaging-based classifier. By comparing pixels that were identified as ECM3 or non-ECM3 with H&E and IHC images, we were also able to observe an association between tissue morphology and the gene expression clusters, showing the ability of our method to capture broad outcome associated features from infrared images. Breast cancer is the most prevalent cancer in women 1 and is estimated to cause over 40,000 deaths annually in the United States. Although cancer has been thought as a consequence of genetic mutations in an aberrant tissue mass, tumor progression is increasingly viewed as functionally interconnected with the surrounding microenvironment 2. Indeed, crosstalk between cancer cells and the tumor microenvironment components [immune cells, stromal cells, and the extracellular matrix (ECM)] plays a major role in regulating several biological processes 3. Differences in ECM-associated gene expression can describe the biological and clinical heterogeneity of breast cancer, especially in terms of prognosis and response to therapy 2. Recent works have identified a subgroup of breast cancers characterized by overexpression of a robust cluster of genes mainly encoding structural ECM proteins, originally referred to as the ECM3 group 4,5. These features indicate an epithelial to mesenchymal transition (EMT) but with accelerated metastatic potential only in the undifferentiated (grade III) phenotype 4,5. Notably, ECM3 classification provides additional information to assess tumor progression 5. It also identifies tumors in which the interplay between myeloid-derived suppressor cells (MDSCs) and the ECM drives the induction of EMT in tumor cells, and suggests a strategy for inhibition of MDSC by aminobisphosphonates that could revert EMT and lead to less aggressive tumor phenotype 6. Even though such molecular classification is of great importance in stratifying patients, it requires multi-step tissue processing and still requires the validation of an algorithm for classification at the single tumor level to be

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An Innovative Platform Merging Elemental Analysis and Ftir Imaging for Breast Tissue Analysis

Cited by 20 publications

References 61 publications

Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy

Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy

Investigation of Biochemical Alterations in Ischemic Stroke Using Fourier Transform Infrared Imaging Spectroscopy—A Preliminary Study

Infrared Spectroscopic Imaging Visualizes a Prognostic Extracellular Matrix-Related Signature in Breast Cancer

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