Ivy Chung

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.

MPA alters metabolic phenotype of endometrial cancer-associated fibroblasts from obese women via IRS2 signaling

Obese women have a higher risk of developing endometrial cancer (EC) than lean women. Besides affecting EC progression, obesity also affects sensitivity of patients to treatment including medroxprogesterone acetate (MPA). Obese women have a lower response to MPA with an increased risk for tumor recurrence. While MPA inhibits the growth of normal fibroblasts, human endometrial cancer-associated fibroblasts (CAFs) were reported to be less responsive to MPA. However, it is still unknown how CAFs from obese women respond to progesterone. CAFs from the EC tissues of obese (CO) and non-obese (CN) women were established as primary cell models. MPA increased cell proliferation and downregulated stromal differentiation genes, including BMP2 in CO than in CN. Induction of IRS2 (a BMP2 regulator) mRNA expression by MPA led to activation of glucose metabolism in CO, with evidence of greater mRNA levels of GLUT6, GAPDH, PKM2, LDHA, and increased in GAPDH enzymatic activity. Concomitantly, MPA increased the mRNA expression of a fatty acid transporter, CD36 and lipid droplet formation in CO. MPA-mediated increase in glucose metabolism genes in CO was reversed with a progesterone receptor inhibitor, mifepristone (RU486), leading to a decreased proliferation. Our data suggests that PR signaling is aberrantly activated by MPA in CAFs isolated from endometrial tissues of obese women, leading to activation of IRS2 and glucose metabolism, which may lead to lower response and sensitivity to progesterone in obese women.