Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression

Abstract Cholangiocarcinoma (CCA) is a prevalent bile duct cancer with limited treatment options. Cisplatin-based chemotherapy is a common approach, but response rates vary. Recently, chromosome aberrations have emerged as predictors of chemotherapy response in various malignancies. This study aimed...

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Main Authors: Sutheemon Techa-ay, Sasithorn Watcharadetwittaya, Raksawan Deenonpoe, Kitti Intuyod, Waleeporn Kaewlert, Anchalee Techasen, Watcharin Loilome, Poramate Klanrit, Manida Suksawat, Kwanjira Chaleekan, Sirinya Sitthirak, Malinee Thanee
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-06851-8
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author Sutheemon Techa-ay
Sasithorn Watcharadetwittaya
Raksawan Deenonpoe
Kitti Intuyod
Waleeporn Kaewlert
Anchalee Techasen
Watcharin Loilome
Poramate Klanrit
Manida Suksawat
Kwanjira Chaleekan
Sirinya Sitthirak
Malinee Thanee
author_facet Sutheemon Techa-ay
Sasithorn Watcharadetwittaya
Raksawan Deenonpoe
Kitti Intuyod
Waleeporn Kaewlert
Anchalee Techasen
Watcharin Loilome
Poramate Klanrit
Manida Suksawat
Kwanjira Chaleekan
Sirinya Sitthirak
Malinee Thanee
author_sort Sutheemon Techa-ay
collection DOAJ
description Abstract Cholangiocarcinoma (CCA) is a prevalent bile duct cancer with limited treatment options. Cisplatin-based chemotherapy is a common approach, but response rates vary. Recently, chromosome aberrations have emerged as predictors of chemotherapy response in various malignancies. This study aimed to identify chromosomal aberrations associated with cisplatin response in CCA. A histoculture drug response assay was conducted on 20 fresh CCA tissues to determine cisplatin sensitivity. In parallel, chromosome aberration analysis was performed using chromosome microarray. Using chromosome microarray analysis on 20 CCA samples, we found distinct chromosomal aberration patterns between cisplatin responders and non-responders. Gains in 18q and 20q, and losses in 1p and 8p were more common in non-responders. Conversely, the responders exhibited gains in 8q and losses in 16q. Our heatmap analysis of log-2 ratio demonstrated difference in various chromosomes including 2, 3p, 5q, 6q, 7, 9p, 11q, 14q, 15q, 18q, 20q, and 22q between the response and the non-response to cisplatin. Further analysis using machine learning with random forest model identified genes like NCOA3, TPK1, CEP57L1, DEPDC5, and PLXNA4 as potential predictors of cisplatin response. Validation in a separate cohort of 33 CCA samples confirmed the association of NCOA3 and DEPDC5 with cisplatin response. Our findings suggest that chromosomal aberrations and specific genes may predict cisplatin response in CCA, potentially guiding personalized treatment strategies.
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spelling doaj-art-9e22e45c874b4599a319a9557d5f328f2025-08-20T03:03:42ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-06851-8Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expressionSutheemon Techa-ay0Sasithorn Watcharadetwittaya1Raksawan Deenonpoe2Kitti Intuyod3Waleeporn Kaewlert4Anchalee Techasen5Watcharin Loilome6Poramate Klanrit7Manida Suksawat8Kwanjira Chaleekan9Sirinya Sitthirak10Malinee Thanee11Cholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityAbstract Cholangiocarcinoma (CCA) is a prevalent bile duct cancer with limited treatment options. Cisplatin-based chemotherapy is a common approach, but response rates vary. Recently, chromosome aberrations have emerged as predictors of chemotherapy response in various malignancies. This study aimed to identify chromosomal aberrations associated with cisplatin response in CCA. A histoculture drug response assay was conducted on 20 fresh CCA tissues to determine cisplatin sensitivity. In parallel, chromosome aberration analysis was performed using chromosome microarray. Using chromosome microarray analysis on 20 CCA samples, we found distinct chromosomal aberration patterns between cisplatin responders and non-responders. Gains in 18q and 20q, and losses in 1p and 8p were more common in non-responders. Conversely, the responders exhibited gains in 8q and losses in 16q. Our heatmap analysis of log-2 ratio demonstrated difference in various chromosomes including 2, 3p, 5q, 6q, 7, 9p, 11q, 14q, 15q, 18q, 20q, and 22q between the response and the non-response to cisplatin. Further analysis using machine learning with random forest model identified genes like NCOA3, TPK1, CEP57L1, DEPDC5, and PLXNA4 as potential predictors of cisplatin response. Validation in a separate cohort of 33 CCA samples confirmed the association of NCOA3 and DEPDC5 with cisplatin response. Our findings suggest that chromosomal aberrations and specific genes may predict cisplatin response in CCA, potentially guiding personalized treatment strategies.https://doi.org/10.1038/s41598-025-06851-8
spellingShingle Sutheemon Techa-ay
Sasithorn Watcharadetwittaya
Raksawan Deenonpoe
Kitti Intuyod
Waleeporn Kaewlert
Anchalee Techasen
Watcharin Loilome
Poramate Klanrit
Manida Suksawat
Kwanjira Chaleekan
Sirinya Sitthirak
Malinee Thanee
Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression
Scientific Reports
title Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression
title_full Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression
title_fullStr Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression
title_full_unstemmed Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression
title_short Predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression
title_sort predicting cisplatin response in cholangiocarcinoma patients using chromosome pattern and related gene expression
url https://doi.org/10.1038/s41598-025-06851-8
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