The first investigation of Wilms' tumour atomic structure-nitrogen and carbon isotopic composition as a novel biomarker for the most individual approach in cancer disease

Abstract

The paper describes a novel approach to investigating Wilms' tumour (nephroblastoma) biology at the atomic level. Isotope Ratio Mass Spectrometry (IRMS) was used to directly assess the isotope ratios of nitrogen and carbon in 84 Wilms' tumour tissue samples from 28 cases representing the histological spectrum of nephroblastoma. Marked differences in nitrogen and carbon isotope ratios were found between nephroblastoma histological types and along the course of cancer disease, with a breakout in isotope ratio of the examined elements in tumour tissue found between stages 2 and 3. Different isotopic compositions with regard to nitrogen and carbon content were observed in blastemal Wilms' tumour, with and without focal anaplasia, and in poorly- and well-differentiated epithelial nephroblastoma. This first assessment of nitrogen and carbon isotope ratio reveals the previously unknown part of Wilms' tumour biology and represents a potential novel biomarker, allowing for a highly individual approach to treating cancer. Furthermore, this method of estimating isotopic composition appears to be the most sensitive tool yet for cancer tissue evaluation, and a valuable complement to established cancer study methods with prospective clinical impact.

Oral Cavity Cancer Tissues Differ in Isotopic Composition Depending on Location and Staging

“…On the basis of the available literature, it can be assumed that changes in the isotopic content of nitrogen and carbon in tissue samples can be used to diagnose and monitor the progression of cancer [5][6][7]. For example, lower levels of 15 N in tumour tissue compared to healthy tissue can indicate decreased cellular protein synthesis in the tumour.…”

Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies

“…No comparison with healthy tissue was done. Taran et al 2016 [ 15 ] measured the δ 15 N of 84 Wilms tumor tissue samples from different nephroblastoma histological types at different stages of this disease. Subsequent stages of the disease varied between 8.11‰ ± 2.73‰ to 8.66‰ ± 0.51‰, with the lowest δ 15 N in stage 3 of the disease.…”

“…Such a 15 N/ 14 N difference could provide an independent metric by which to identify and characterize cancerous tissue, as well as to study the N metabolism of different cancer types. On a statistical basis, one study of cancer in human patients has observed a significantly lower 15 N/ 14 N in tumor relative to healthy tissue [ 18 ] while other studies have not [ 15 , 17 ]. For practical reasons and due to the abiding consideration of patient welfare, none of these studies undertook comparisons within individual organisms.…”

Characteristic of Oral Squamous Cell Carcinoma Tissues Using Isotope Ratio Mass Spectrometry

“…The head and neck cancers’ occurrence keeps rising so it is essential to establish if spectrometry, this new possibility of evaluation, can be as helpful as other types of diagnosing malignancies. Some studies have already indicated usefulness of IRMS in case of Wilms’ tumour, hepatoblastoma or rhabdomyosarcoma [ 19 , 22 , 32 ]. Numerous articles prove that, based on neoplasm’s isotopic composition and ratios, it is possible to picture its abnormal metabolism that reflects the course of the disease [ 19 ].…”

“…Scientific research supports the statement that it is possible to characterise the origin of damaged or healthy cells by means of isotope ratio mass spectrometry [ 21 , 22 ]. Currently, it is used for laboratory diagnostics, genetics, biotechnology or proteomics [ 23 , 24 , 25 , 26 , 27 ].…”