title: Classification of Gemcitabine resistant Cholangiocarcinoma cell lines using synchrotron FTIR microspectroscopy.
abstract: Cholangiocarcinoma (CCA), a cancer of bile duct epithelium, is a major health problem in Thailand especially in the northeast. Overall treatment outcomes have not shown much improvement because the disease is usually detected at an advanced stage and often shows chemotherapeutic resistance. High-throughput Fourier Transform Infrared (FTIR) microspectroscopy can be used for cell classification and has the potential to diagnose cancer and possibly predict chemo-response. This study was aimed to differentiate gemcitabine-sensitive and gemcitabine-resistant induction in two CCA cell lines (KKU-M139 and KKU-M214) and xenograft tissues using synchrotron-FTIR microspectroscopy. Partial Least Squares Discriminant Analysis (PLS-DA) could discriminate between chemo-sensitive and chemo-resistant cells in the FTIR fingerprint spectral region (1800-1000 cm-1) with more than 90% sensitivity and specificity. The chemo-resistant and chemo-sensitive phenotypes were different in protein (amide I, amide II), lipids (carbonyl group and CH3deformation) and phosphodiester from nucleic acids. Additionally, spectra from xenograft tissues showed similar results to the cell line study with marked differences between chemo-resistant and chemo-sensitive CCA tissues, and PLS-DA could discriminate the chemotherapeutic response with 98% sensitivity and specificity. This is the first study to demonstrate the use of FTIR microspectroscopy to assess chemo-response both in vitro and in vivo.
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.|Liver Fluke and Cholangiocarcinoma Research center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Biomedical Sciences, Graduate School,, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Molin
authors.initials: M
authors.lastname: Wongwattanakul
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chariya
authors.initials: C
authors.lastname: Hahnvajanawong
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Patcharaporn
authors.initials: P
authors.lastname: Tippayawat
authors.affiliation: Synchrotron Light Research Institute (Public Organization), Nakhon Ratchasima, Thailand.
authors.forename: Sirinart
authors.initials: S
authors.lastname: Chio-Srichan
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.|Liver Fluke and Cholangiocarcinoma Research center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chanvit
authors.initials: C
authors.lastname: Leelayuwat
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.|Liver Fluke and Cholangiocarcinoma Research center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Temduang
authors.initials: T
authors.lastname: Limpaiboon
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.|Liver Fluke and Cholangiocarcinoma Research center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Patcharee
authors.initials: P
authors.lastname: Jearanaikoon
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia.|Centre for Biospectroscopy, School of Chemistry, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Heraud
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging* / Q000188:drug therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008853:Microscopy; D009368:Neoplasm Transplantation; D010641:Phenotype; D012680:Sensitivity and Specificity; D017550:Spectroscopy, Fourier Transform Infrared / Q000295:instrumentation; D017356:Synchrotrons; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Cholangiocarcinoma; Synchrotron-FTIR; animal model; cell lines; chemo-resistance