Metabolically Active Zones Involving Fatty Acid Elongation Delineated by DESI-MSI Correlate with Pathological and Prognostic Features of Colorectal Cancer

Martin Kaufmann; Natasha Iaboni; Amoon Jamzad; David Hurlbut; Kevin Yi Mi Ren; John F Rudan; Parvin Mousavi; Gabor Fichtinger; Sonal Varma; Antonio Caycedo-Marulanda; Christopher J B Nicol

doi:10.3390/metabo13040508

Metabolically Active Zones Involving Fatty Acid Elongation Delineated by DESI-MSI Correlate with Pathological and Prognostic Features of Colorectal Cancer

Metabolites. 2023 Mar 31;13(4):508. doi: 10.3390/metabo13040508.

Authors

Martin Kaufmann^{1

2}, Natasha Iaboni³, Amoon Jamzad⁴, David Hurlbut³, Kevin Yi Mi Ren³, John F Rudan¹, Parvin Mousavi⁴, Gabor Fichtinger⁴, Sonal Varma³, Antonio Caycedo-Marulanda^{1

5}, Christopher J B Nicol^{3

6}

Affiliations

¹ Department of Surgery, Kingston Health Sciences Centre, Kingston, ON K7L 2V7, Canada.
² Gastrointestinal Diseases Research Unit, Kingston Health Sciences Center, Kingston, ON K7L 2V7, Canada.
³ Department of Pathology and Molecular Medicine, Queen's University and Kingston Health Sciences Centre, Kingston, ON K7L 3N6, Canada.
⁴ School of Computing, Queen's University, Kingston, ON K7L 2N8, Canada.
⁵ Orlando Health Colon and Rectal Institute, Orlando, FL 32806, USA.
⁶ Queen's Cancer Research Institute, Division of Cancer Biology and Genetics, Kingston, ON K7L 3N6, Canada.

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths. Despite recent advances, five-year survival rates remain largely unchanged. Desorption electrospray ionization mass spectrometry imaging (DESI) is an emerging nondestructive metabolomics-based method that retains the spatial orientation of small-molecule profiles on tissue sections, which may be validated by 'gold standard' histopathology. In this study, CRC samples were analyzed by DESI from 10 patients undergoing surgery at Kingston Health Sciences Center. The spatial correlation of the mass spectral profiles was compared with histopathological annotations and prognostic biomarkers. Fresh frozen sections of representative colorectal cross sections and simulated endoscopic biopsy samples containing tumour and non-neoplastic mucosa for each patient were generated and analyzed by DESI in a blinded fashion. Sections were then hematoxylin and eosin (H and E) stained, annotated by two independent pathologists, and analyzed. Using PCA/LDA-based models, DESI profiles of the cross sections and biopsies achieved 97% and 75% accuracies in identifying the presence of adenocarcinoma, using leave-one-patient-out cross validation. Among the m/z ratios exhibiting the greatest differential abundance in adenocarcinoma were a series of eight long-chain or very-long-chain fatty acids, consistent with molecular and targeted metabolomics indicators of de novo lipogenesis in CRC tissue. Sample stratification based on the presence of lympovascular invasion (LVI), a poor CRC prognostic indicator, revealed the abundance of oxidized phospholipids, suggestive of pro-apoptotic mechanisms, was increased in LVI-negative compared to LVI-positive patients. This study provides evidence of the potential clinical utility of spatially-resolved DESI profiles to enhance the information available to clinicians for CRC diagnosis and prognosis.

Keywords: biopsy; colorectal cancer; desorption electrospray ionization mass spectrometry imaging; histopathology; long chain fatty acids; lymphovascular invasion; prognostic markers.

Abstract

Grants and funding