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Cancer Res. 2019 Apr 15;79(8):2054-2064. doi: 10.1158/0008-5472.CAN-18-2732. Epub 2019 Feb 28.

Label-Free Raman Spectroscopy Reveals Signatures of Radiation Resistance in the Tumor Microenvironment.

Author information

1
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland.
2
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas.
3
Division of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
4
Division of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
5
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas. ibarman@jhu.edu nrajaram@uark.edu.
6
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland. ibarman@jhu.edu nrajaram@uark.edu.
7
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
8
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
#
Contributed equally

Abstract

Delay in the assessment of tumor response to radiotherapy continues to pose a major challenge to quality of life for patients with nonresponsive tumors. Here, we exploited label-free Raman spectroscopic mapping to elucidate radiation-induced biomolecular changes in tumors and uncovered latent microenvironmental differences between treatment-resistant and -sensitive tumors. We used isogenic radiation-resistant and -sensitive A549 human lung cancer cells and human head and neck squamous cell carcinoma (HNSCC) cell lines (UM-SCC-47 and UM-SCC-22B, respectively) to grow tumor xenografts in athymic nude mice and demonstrated the molecular specificity and quantitative nature of Raman spectroscopic tissue assessments. Raman spectra obtained from untreated and treated tumors were subjected to chemometric analysis using multivariate curve resolution-alternating least squares (MCR-ALS) and support vector machine (SVM) to quantify biomolecular differences in the tumor microenvironment. The Raman measurements revealed significant and reliable differences in lipid and collagen content postradiation in the tumor microenvironment, with consistently greater changes observed in the radiation-sensitive tumors. In addition to accurately evaluating tumor response to therapy, the combination of Raman spectral markers potentially offers a route to predicting response in untreated tumors prior to commencing treatment. Combined with its noninvasive nature, our findings provide a rationale for in vivo studies using Raman spectroscopy, with the ultimate goal of clinical translation for patient stratification and guiding adaptation of radiotherapy during the course of treatment. SIGNIFICANCE: These findings highlight the sensitivity of label-free Raman spectroscopy to changes induced by radiotherapy and indicate the potential to predict radiation resistance prior to commencing therapy.

PMID:
30819665
PMCID:
PMC6467810
[Available on 2020-04-15]
DOI:
10.1158/0008-5472.CAN-18-2732

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