Amira Hajirah Abd Jamil

Detecting metabolic signatures in endometrial cancer: potential applications of Raman spectroscopy

Endometrial cancer (EC) is intricately linked to obesity, with metabolic reprogramming increasingly established to drive oncogenic transformation and influence treatment outcomes. Implementation of early detection strategy significantly reduces morbidity and mortality; however, screening strategies lack the required sensitivity, specificity, and accuracy to be successfully implemented in clinical practice. Current diagnostic approaches are also invasive, costly, and time-consuming, highlighting a gap in developing diagnostic and screening alternatives for EC among high-risk individuals, especially with sensitivity to capture cancer-specific changes. Raman Spectroscopy is an emerging tool in medical diagnostics. By exploiting the atomic vibrational absorption induced by the interaction of light with a biological sample, a unique spectral response namely a "metabolite fingerprint" can be generated. This nondestructive technique combined with multivariate statistical analysis can characterize metabolic discrimination between cancerous and healthy samples, demonstrating a promising role in cancer screening, diagnosis, and monitoring of treatment outcomes. This review aimed to collate available evidence on Raman's ability to capture metabolic abnormalities, particularly cancer-specific metabolites during malignant transformation and therapeutic resistance. Given that cellular metabolism is altered in EC, this review will provide insight into its potential applications for EC screening, diagnosis, and prospects, especially for monitoring treatment outcomes among high-risk patients.

Distinct Lipid Phenotype of Cancer-Associated Fibroblasts (CAFs) Isolated From Overweight/Obese Endometrial Cancer Patients as Assessed Using Raman Spectroscopy

Obesity is strongly linked with increased risk and poorer prognosis of endometrial cancer (EC). Cancer-associated fibroblasts (CAFs) are activated fibroblasts that form a large component of the tumor microenvironment and undergo metabolic reprogramming to provide critical metabolites for tumor growth. However, it is still unknown how obesity, characterized by a surplus of free fatty acids drives the modifications of CAFs lipid metabolism which may provide the mechanistic link between obesity and EC progression. The present study aims to evaluate the utility of Raman spectroscopy, an emerging nondestructive analytical tool to detect signature changes in lipid metabolites of CAFs from EC patients with varying body mass index. We established primary cultures of fibroblasts from human EC tissues, and CAFs of overweight/obese and nonobese women using antibody-conjugated magnetic beads isolation. These homogeneous fibroblast cultures expressed fibroblast markers, including α-smooth muscle actin and vimentin. Analysis was made in the Raman spectra region best associated with cancer progression biochemical changes in lipids (600–1800 cm–1 and 2800–3200 cm–1). Direct band analysis and ratiometric analysis were conducted to extract information from the Raman spectrum. Present results demonstrated minor shifts in the CH2 symmetric stretch of lipids at 2879 cm–1 and CH3 asymmetric stretching from protein at 2932 cm–1 in the overweight/obese CAFS compared to nonobese CAFs, indicating increased lipid content and a higher degree of lipid saturation. Principal component analysis showed that CAFs from overweight/obese and nonobese EC patients can be clearly distinguished indicating the capability of Raman spectroscopy to detect changes in biochemical components. Our results suggest Raman spectroscopy supported by chemometric analysis is a reliable technique for characterizing metabolic changes in clinical samples, providing an insight into obesity-driven alteration in CAFs, a critical stromal component during EC tumorigenesis.