FTIR-ATR Spectroscopic Signatures of Systemic Metabolic Reprogramming and Nucleic Acid Alterations in Uninvolved Liver Induced by Ectopic Carcinoma

Background: Malignant tumours remodel not only the local microenvironment but also host systemic metabolism. Distant organs, above all the liver as a central metabolic hub, undergo reprogramming under the influence of circulating tumour- and inflammation-derived mediators — even when the liver itself is not the site of the primary tumour. Fourier-transform infrared spectroscopy in attenuated total reflection mode (FTIR-ATR) provides integrative information on the molecular composition of tissues and is therefore suitable for registering such remote host effects. Objective: To compare the FTIR-ATR spectral characteristics of uninvolved liver from healthy mice and from mice bearing an ectopic (subcutaneous) carcinoma, and to identify spectral signatures of the systemic impact of the tumour on the organism. Methods: Female C57BL/6J mice aged 11 weeks were injected subcutaneously with murine carcinoma cells of the RIL-175 line in a PBS : Matrigel mixture (2×106 cells; tumour group, n = 6) or with an equivalent volume of the cell-free vehicle (control, n = 10). Uninvolved liver collected at necropsy (an organ remote from the inoculation site) was dehydrated in ascending concentrations of ethanol, dried, and analysed on a Nicolet iS50 spectrometer (4000–400 cm–1, three technical replicates per organ). The spectra were smoothed (Savitzky – Golay filter), truncated to the 900–1720 cm–1 range, baseline-corrected, and normalised. Common peaks were selected by consensus voting based on the second derivative, and each spectrum was approximated by a sum of pseudo-Voigt functions. Height, full width at half maximum (FWHM), area, and the mixing coefficient η were compared between the groups (Mann — Whitney test, Cliff’s δ, point-biserial correlation; Benjamini — Hochberg correction, FDR < 0,05). Results: Consensus voting yielded 56 common peaks and 224 features; the quality of approximation was high (R2 = 0.99997). Sixteen peaks differed significantly between the groups according to both statistical approaches. In the uninvolved liver of tumour-bearing animals, the bands assigned to the sugar–phosphate backbone of nucleic acids and to asymmetric stretching vibrations of PO2– (920, 1055, 1187, 1201 cm–1) were elevated, whereas the carbohydrate (glycogen) band at 1046 cm–1 was decreased. In the Amide I and Amide II regions, a redistribution of protein secondary structure was observed: in tumour-bearing animals the contribution of the α-helix (1650 cm–1) was smaller, while intramolecular β-sheet structures and β-turns (1638, 1683 cm–1) were greater. Conclusions: FTIR-ATR reveals a consistent set of spectral changes in the uninvolved liver of mice bearing an ectopic carcinoma. These changes reflect systemic metabolic reprogramming of the host organism under the influence of a distant tumour, rather than local neoplastic involvement of the liver.