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oai:repisalud.isciii.es:20.500.12105/232332024-11-28T19:43:36Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Garate, Jone author Maimó-Barceló, Albert author Bestard-Escalas, Joan author Fernandez, Roberto author Pérez-Romero, Karim author Martinez Ortega, Marco Antonio author Payeras Capo, Maria Antonia author Lopez, Daniel H author Fernández, José Andrés author Barceló-Coblijn, Gwendolyn author 2021-03-17 Even though colorectal cancer (CRC) is one of the most preventable cancers, it is one of the deadliest, and recent data show that the incidence in people <50 years has unexpectedly increased. While new techniques for CRC molecular classification are emerging, no molecular feature is as yet firmly associated with prognosis. Imaging mass spectrometry (IMS) lipidomic analyses have demonstrated the specificity of the lipid fingerprint in differentiating pathological from healthy tissues. During IMS lipidomic analysis, the formation of ionic adducts is common. Of particular interest is the [Na+]/[K+] adduct ratio, which already functions as a biomarker for homeostatic alterations. Herein, we show a drastic shift of the [Na+]/[K+] adduct ratio in adenomatous colon mucosa compared to healthy mucosa, suggesting a robust increase in K+ levels. Interrogating public databases, a strong association was found between poor diagnosis and voltage-gated potassium channel subunit beta-2 (KCNAB2) overexpression. We found this overexpression in three CRC molecular subtypes defined by the CRC Subtyping Consortium, making KCNAB2 an interesting pharmacological target. Consistently, its pharmacological inhibition resulted in a dramatic halt in commercial CRC cell proliferation. Identification of potential pharmacologic targets using lipid adduct information emphasizes the great potential of IMS lipidomic techniques in the clinical field. Garate J, Maimó-Barceló A, Bestard-Escalas J, Fernández R, Pérez-Romero K, Martínez MA, et al. A Drastic Shift in Lipid Adducts in Colon Cancer Detected by MALDI-IMS Exposes Alterations in Specific K+ Channels. Cancers. 2021;13(6):1350. 10.3390/cancers13061350 2072-6694 Cancers http://hdl.handle.net/20.500.13003/18460 33802791 L2006757937 2-s2.0-85102574941 https://hdl.handle.net/20.500.12105/23233 634371500001 Colorectal cancer Lipidomics Ion adducts Potassium channels A Drastic Shift in Lipid Adducts in Colon Cancer Detected by MALDI-IMS Exposes Alterations in Specific K+ Channels