Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer

Abstract

Background Radiation therapy is a standard form of treating non-small cell lung cancer, however, local recurrence is a major issue with this type of treatment. A better understanding of the metabolic response to radiation therapy may provide insight into improved approaches for local tumour control. Cyclic hypoxia is a well-established determinant that influences radiation response, though its impact on other metabolic pathways that control radiosensitivity remains unclear. Methods We used an established Raman spectroscopic (RS) technique in combination with immunofluorescence staining to measure radiation-induced metabolic responses in human non-small cell lung cancer (NSCLC) tumour xenografts. Tumours were established in NOD.CB17-Prkdc scid /J mice, and were exposed to radiation doses of 15 Gy or left untreated. Tumours were harvested at 2 h, 1, 3 and 10 days post irradiation. Results We report that xenografted NSCLC tumours demonstrate rapid and stable metabolic changes, following exposure to 15 Gy radiation doses, which can be measured by RS and are dictated by the extent of local tissue oxygenation. In particular, fluctuations in tissue glycogen content were observed as early as 2 h and as late as 10 days post irradiation. Metabolically, this signature was correlated to the extent of tumour regression. Immunofluorescence staining for γ–H2AX, pimonidazole and carbonic anhydrase IX (CAIX) correlated with RS-identified metabolic changes in hypoxia and reoxygenation following radiation exposure. Conclusion Our results indicate that RS can identify sequential changes in hypoxia and tumour reoxygenation in NSCLC, that play crucial roles in radiosensitivity. Electronic supplementary material The online version of this article (10.1186/s12885-019-5686-1) contains supplementary material, which is available to authorized users.

Novel Diagnostic and Therapeutic Techniques Reveal Changed Metabolic Profiles in Recurrent Focal Segmental Glomerulosclerosis 

“…Raman spectra are directly related to the biochemical composition of tissues [42][43][44] . In the past, Raman was used to detect metabolomic changes in different cancers 45,46 . However, Raman spectroscopy was never used before to study metabolomics in FSGS.…”

Raman spectroscopy and group and basis-restricted non negative matrix factorisation identifies radiation induced metabolic changes in human cancer cells

“…The metabolism of glycogen involves an array of complex signalling pathways, many of which can be directly related to tumour progression [8][9][10][11][12] . Increase in glycogen content within tumour cells post radiation treatment is thought to provide metabolic precursors which protect against hypoxia and other forms of stress 13 .…”

Unveiling Cancer Metabolism through Spontaneous and Coherent Raman Spectroscopy and Stable Isotope Probing

“…Roman et al reported a change in the lipid composition and concentration in prostate cancer cells after X-ray radiation [ 80 ]. Similarly, metabolic alterations of cancer cells after radiation were also seen in nasopharyngeal cancer [ 79 ], non-small lung cancer [ 83 ], and glioblastoma [ 82 ]. A study by Milligan et al found different biochemical responses between radio-resistant and radio-sensitive cell types in lung (H460), breast (MCF7), and prostate (LNCaP) cells [ 81 ].…”

“…Besides chemotherapy, radiotherapy is the mainstay of the treatment for a range of types of cancer. Monitoring radiation-induced cellular response of cancer at both cell and tissue levels was studied by Raman spectroscopy [79][80][81][82][83]. Roman et al reported a change in the lipid composition and concentration in prostate cancer cells after X-ray radiation [80].…”