Screening of important metabolites and KRAS genotypes in colon cancer using secondary ion mass spectrometry

Abstract

Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) is an imaging‐based analytical technique that can characterize the surfaces of biomaterials. We used TOF‐SIMS to identify important metabolites and oncogenic KRAS mutation expressed in human colorectal cancer (CRC). We obtained 540 TOF‐SIMS spectra from 180 tissue samples by scanning cryo‐sections and selected discriminatory molecules using the support vector machine (SVM) algorithm. Each TOF‐SIMS spectrum contained nearly 860,000 ion profiles and hundreds of spectra were analyzed; therefore, reducing the dimensionality of the original data was necessary. We performed principal component analysis after preprocessing the spectral data, and the principal components (20) of each spectrum were used as the inputs of the SVM algorithm using the R package. The performance of the algorithm was evaluated using the receiver operating characteristic (ROC) area under the curve (AUC) (0.9297). Spectral peaks (m/z) corresponding to discriminatory molecules used to classify normal and tumor samples were selected according to p‐value and were assigned to arginine, α‐tocopherol, and fragments of glycerophosphocholine. Pathway analysis using these discriminatory molecules showed that they were involved in gastrointestinal disease and organismal abnormalities. In addition, spectra were classified according to the expression of KRAS somatic mutation, with 0.9921 AUC. Taken together, TOF‐SIMS efficiently and simultaneously screened metabolite biomarkers and performed KRAS genotyping. In addition, a machine learning algorithm was provided as a diagnostic tool applied to spectral data acquired from clinical samples prepared as frozen tissue slides, which are commonly used in a variety of biomedical tests.

Advanced progress of spatial metabolomics in head and neck cancer research

“…SIMS can be coupled with diverse mass analyzers, including Time-of-Flight (ToF) and Fourier Transform Ion Cyclotron Resonance (FTICR), thereby augmenting its ability to scrutinize intricate biological systems [62] . Just as in the case of MALDI and DESI, SIMS-MSI holds widespread utility in cancer research, encompassing studies on colon cancer, breast cancer, medulloblastoma, and others [63] , [64] , [65] .…”

Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations

“…Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. The KRAS oncogene, mutated in approximately 40% of CRC patients [ 1 ], is both a prognostic and predictive biomarker for which treatment is tailored. The incidence of tumors with KRAS mutations is higher on the right-side of the colon and occurs more frequently in female patients than males [ 2 ].…”

Simultaneous Multiplexed Imaging of Biomolecules in Transgenic Mouse Brain Tissues Using Mass Spectrometry Imaging: A Multi-omic Approach

“…Time-of-flight secondary ion MS (ToF-SIMS) is one of the major MS-based imaging tools providing valuable chemical information of tissues at subcellular resolution without requiring matrix treatment. , Particularly, it has been used to observe the distribution of lipids and metabolites, − to diagnose diseases and to discover biomarkers. − However, despite its advantages, the ToF-SIMS technique also has difficulties in imaging proteins or mRNA in tissues on account of their large sizes. , …”