Cholangiocarcinoma – current classification and challenges towards personalised medicine

Byrling, Johannes; Andersson, Bodil; Andersson, Roland; Markó-Varga, György

doi:10.3109/00365521.2015.1127409

Cited by 7 publications

(4 citation statements)

References 25 publications

(24 reference statements)

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“…The classification of CCA is based on anatomical location including intrahepatic and extrahepatic CCA, where extrahepatic CCA is subdivided into perihilar and distal CCA. 4 The frequent forms of intrahepatic CCA in Thailand are intraductal growth, periductal infiltrating and massforming types, while the vast majority of perihilar and distal CCA are mucinous adenocarcinoma. 1,5 CCA has been suggested to be stemmed from diverse cell origins, such as hepatic stem cells, various stages of cholangiocytes and peribiliary gland cells.…”

Section: Introductionmentioning

confidence: 99%

Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand

et al. 2017

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Cholangiocarcinoma is a rare type of cancer which is an increasingly discernible health threat. The disease is usually very difficult in diagnosis and various treatment modalities are typically not effective. Cholangiocarcinoma is a complex and very heterogeneous malignancy characterized by tumor location, different risk factors, molecular profiling, and prognosis. Cancer cell lines represent an important tool for investigation in various aspects of tumor biology and molecular therapeutics. We established two cell lines, KKU-452 and KKU-023, which were derived from patients residing in the endemic area of liver fluke infection in Thailand. Both of tumor tissues have gross pathology of perihilar and intrahepatic mass-forming cholangiocarcinoma. Two cell lines were characterized for their biological, molecular and genetic properties. KKU-452 and KKU-023 cells are both adherent cells with epithelium morphology, but have some differences in their growth pattern (a doubling time of 17.9 vs 34.8 h, respectively) and the expression of epithelial bile duct markers, CK7 and CK19. Cytogenetic analysis of KKU-452 and KKU-023 cells revealed their highly complex karyotypes; hypertriploid and hypotetraploid, respectively, with multiple chromosomal aberrations. Both cell lines showed mutations in p53 but not in KRAS. KKU-452 showed a very rapid migration and invasion properties in concert with low expression of E-cadherin and high expression of N-cadherin, whereas KKU-023 showed opposite characters. KKU-023, but not KKU-452, showed in vivo tumorigenicity in xenografted nude mice. Those two established cholangiocarcinoma cell lines with unique characters may be valuable for better understanding the process of carcinogenesis and developing new therapeutics for the patients.

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Section: Introductionmentioning

confidence: 99%

Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand

et al. 2017

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“…To develop such a model, new sensors, methods, platforms, and unique biomarkers for diagnosis, and therapeutic outcome prediction are required. 29 There is still a need for devices and sensors able to provide good quality reports of relevant information on patient health. For instance, no thoroughly validated device for measuring cardiac output is currently available.…”

Section: Discussionmentioning

confidence: 99%

Transforming big data into computational models for personalized medicine and health care

Najarian

2016

Dialogues in Clinical Neuroscience

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Health care systems generate a huge volume of different types of data. Due to the complexity and challenges inherent in studying medical information, it is not yet possible to create a comprehensive model capable of considering all the aspects of health care systems. There are different points of view regarding what the most efficient approaches toward utilization of this data would be. In this paper, we describe the potential role of big data approaches in improving health care systems and review the most common challenges facing the utilization of health care big data.

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“…Mounting evidence points to a significant difference between the different subtypes with regards to not only clinical management but also tumor biology and molecular characteristics [3,6,7]. However, the majority of previous biomarker studies do not take this subclassification into account [3,8]. Currently, only one biomarker, namely, plasma carbohydrate antigen 19-9 (CA 19-9) is in clinical use for the diagnosis of CCA.…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

Byrling

Kristl

et al. 2020

J Transl Med

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Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.

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Cholangiocarcinoma – current classification and challenges towards personalised medicine

Cited by 7 publications

References 25 publications

Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand

Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand

Transforming big data into computational models for personalized medicine and health care

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

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