Spectroscopic diagnosis and metabolite characterization of cisplatin resistance regulated by FDFT1 in bladder cancer tissue

• Main Authors: Kanmalar, M., Kamal, Raihan, Sani, Siti Fairus Abdul, Pathmanathan, Dharini, Said, Nur Akmarina Mohd, Paramanantham, Yogaambikai, Abd Jamil, Amira Hajirah, Mun, K.S., Kuppusamy, S., Almugren, K.S., Almajid, Hadeel F., Bradley, D.A.
• Format: Article
• Published: Elsevier 2024
• Subjects: QD Chemistry; T Technology (General)
• Online Access: http://eprints.um.edu.my/45112/; https://doi.org/10.1016/j.apradiso.2024.111372

As is the case for most solid tumours, chemotherapy remains the backbone in the management of metastatic disease. However, the occurrence of chemotherapy resistance is a cause to worry, especially in bladder cancer. Extensive evidence indicates molecular changes in bladder cancer cells to be the underlying cause of chemotherapy resistance, including the reduced expression of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) - a gene involved in cholesterol biosynthesis. This can likely be a hallmark in examining the resistance and sensitivity of chemotherapy drugs. This work performs spectroscopic analysis and metabolite characterization on resistant, sensitive, stable-disease and healthy bladder tissues. Raman spectroscopy has detected peaks at around 1003 cm-1 (squalene), 1178 cm-1 (cholesterol), 1258 cm-1 (cholesteryl ester), 1343 cm-1 (collagen), 1525 cm-1 (carotenoid), 1575 cm-1 (DNA bases) and 1608 cm-1 (cytosine). The peak parameters were examined, and statistical analysis was performed on the peak features, attaining significant differences between the sample groups. Small-angle x-ray scattering (SAXS) measurements observed the triglyceride peak together with 6th, 7th and 8th - order collagen peaks; peak parameters were also determined. Neutron activation analysis (NAA) detected seven trace elements. Carbon (Ca), magnesium (Mg), chlorine (Cl) and sodium (Na) have been found to have the greatest concentration in the sample groups, suggestive of a role as a biomarker for cisplatin resistance studies. Results from the present research are suggested to provide an important insight into understanding the development of drug resistance in bladder cancer, opening up the possibility of novel avenues for treatment through personalised interventions.