Raman Spectroscopy Reveals Key Insights into Obesity-Driven Changes in Endometrial Cancer

Researchers at Universiti Malaya in Kuala Lumpur, Malaysia have harnessed the power of Raman spectroscopy to investigate the metabolic changes occurring in cancer-associated fibroblasts (CAFs) obtained from endometrial cancer (EC) patients with varying body mass indexes (BMIs) (1). The study, published in Applied Spectroscopy, delves into the lipid phenotype of CAFs, aiming to elucidate the connection between obesity and EC progression.

Endometrial cancer cells (adenocarcinoma) in the uterus or cervix (womb neck) - closeup view 3d illustration | Image Credit: © LASZLO

CAFs are activated fibroblasts that constitute a significant part of the tumor microenvironment, undergoing metabolic reprogramming to supply critical metabolites essential for tumor growth. Obesity has long been associated with an increased risk of endometrial cancer and poorer prognoses, but the underlying mechanisms remain unclear. The researchers sought to unravel how obesity, characterized by an excess of free fatty acids, influences the lipid metabolism of CAFs and contributes to EC progression.

To carry out the study, the scientists established primary fibroblast cultures from human EC tissues and isolated CAFs from either overweight or obese as well as nonobese women using antibody-conjugated magnetic bead isolation. These homogeneous fibroblast cultures were confirmed to express specific fibroblast markers, including α-smooth muscle actin and vimentin, ensuring their relevance to the study.

Antibody-conjugated magnetic bead isolation is a technique used in biotechnology to selectively isolate specific target molecules from complex biological samples. It involves the attachment of antibodies to magnetic beads, forming antibody-bead complexes. When introduced to a sample, these complexes can bind specifically to the target molecules or cells of interest. By applying a magnetic field, the bead-bound target molecules are separated from the rest of the sample, allowing for efficient and highly specific isolation of the desired cells.

The analysis focused on the Raman spectra regions associated with biochemical changes in lipids (600–1800 cm^–1 and 2800–3200 cm^–1). By employing direct band and ratiometric analyses, the researchers extracted valuable information from the Raman spectra, revealing 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 CAFs from the overweight or obese patients compared to their nonobese counterparts. These shifts indicated an increased lipid content and a higher degree of lipid saturation in CAFs of overweight and obese individuals.

Through principal component analysis, the researchers demonstrated the capability of Raman spectroscopy to clearly distinguish CAFs from overweight or obese and nonobese EC patients based on their biochemical components. This finding showcased the potential of Raman spectroscopy to effectively detect changes in biochemical components.

The study's findings offer crucial insights into the role of cancer-associated fibroblasts and their lipid metabolism in obesity-driven alterations during endometrial cancer tumorigenesis. The combination of Raman spectroscopy with chemometric analysis emerged as a reliable technique for characterizing metabolic changes in clinical samples, providing valuable insights into the intricate interplay between obesity and endometrial cancer progression.

The application of Raman spectroscopy in investigating the lipid phenotype of cancer-associated fibroblasts holds promise in the realm of cancer research and personalized medicine. By identifying specific metabolic changes associated with obesity, this nondestructive analytical method could serve as a diagnostic and prognostic tool in stratifying patients based on their BMI profiles, potentially leading to more targeted and effective treatment approaches for endometrial cancer. Additionally, Raman spectroscopy may fit applications in the study of other cancer types and their associations with metabolic alterations in the tumor microenvironment, opening new avenues for understanding and combating various forms of cancer.

Reference

(1) Yeu, T.H.; Omar, I.S.; Jamil, A.H.A., et al. Distinct Lipid Phenotype of Cancer-Associated Fibroblasts (CAFs) Isolated From Overweight/Obese Endometrial Cancer Patients as Assessed Using Raman Spectroscopy. Appl. Spectrosc. 2023, 77 (7), 723–733. DOI: 10.1177/00037028231182721