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Biochemical Indicators of Cholangiocarcinoma

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Diagnosis and Management of Cholangiocarcinoma

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Abstract

Cholangiocarcinoma (CCA) is one of the most frequent epithelial liver tumors and a significant problem with regard to clinical management. The causes of CCA are heterogeneous and associated with the geographic factors, with particularly high incidence in East Asian countries. Patients with CCA often suffer from adverse clinical outcomes and a poor prognosis, much of which is due to the lack of efficient diagnostic tools and biomarkers. Moreover, genome-wide screening of gene alterations and omics analyses demonstrate the highly diverse nature of oncogenic genetic factors among individual CCA tumor cells. Here, we summarize the current approaches to identifying CCA tumor biomarkers and other biochemical indicators for diagnosis and selection of appropriate treatment as a step toward precision medicine with personalized patient care and a goal of improved clinical outcomes.

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Abbreviations

AFP:

Alpha-fetoprotein

AID:

Activation-induced cytidine deaminase

AMPN:

Aminopeptidase N

APC:

Adenomatous polyposis coli

APOBEC:

Apolipoprotein B mRNA editing enzyme

ARID1A:

AT-rich interactive domain-containing protein 1A

AUC:

Area under the curve

BAP1:

BRCA1-associated protein 1

BAR:

Beta-catenin/armadillo-related protein

B-CADHERIN:

Brain cadherin (catenin cell-cell adhesion complex)

BCL2:

B-cell lymphoma 2

BCLX5:

B-cell lymphoma-extra large 5

BCLXL:

B-cell lymphoma-extra large

BRAF:

v-Raf murine sarcoma viral oncogene homolog

BRCA1:

Breast cancer susceptibility gene I

BRCA2:

Breast cancer susceptibility gene II

BSEP:

Bile salt export pump

CA 19-9:

Carbohydrate antigen 19-9

CCA:

Cholangiocarcinoma

CCND1:

Cyclin D1

CDC6:

Cell division cycle 6

CDK6:

Cyclin-dependent kinase 6

CDKN2A:

Cyclin-dependent kinase inhibitor 2

CEA:

Carcinoembryonic antigen

cfDNA:

Cell-free DNA

COX-2:

Cyclooxygenase 2

CTC:

Circulating tumor cell

CYP1A2:

Cytochrome P450 family 1 subfamily A member 2

dCCA:

Distal cholangiocarcinoma

EGFR:

Epidermal growth factor receptor

EpCAM:

Epithelial cell adhesion molecule

ERB-2:

Erb-B2 receptor tyrosine kinase 2

EVs:

Extracellular vesicles

FBXW7:

F-box and WD repeat domain containing 7

FGF19:

Fibroblast growth factor 19

FGFR2:

Fibroblast growth factor receptor 2

FIC1:

Familial intrahepatic cholestasis type 1

FXR:

Farnesoid X receptor

GANP:

Germinal center-associated nuclear protein

GSTO1:

Glutathione S-transferase omega 1

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HOXD9:

Homeobox protein Hox-D9

iCCA:

Intrahepatic cholangiocarcinoma

IDH1:

Isocitrate dehydrogenase [ADP(+) 1]

IDH2:

Isocitrate dehydrogenase [ADP(+) 2]

KEAP1:

Kelch-like ECH-associated protein 1

K-RAS:

Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

LTO1:

LTO1 maturation factor of ABCE1

mAb:

Monoclonal antibody

MCL1:

Induced myeloid leukemia cell differentiation protein

MDM2:

Mouse double minute 2 homolog

MDR3:

Multidrug resistance gene 3

miR:

MicroRNA

MRP2:

Multidrug resistance-associated protein 2

MTHFR:

Methylenetetrahydrofolate reductase

MVs:

Microvesicles

MYC:

v-Myc myelocytomatosis viral oncogene homolog

NAT2:

Arylamine N-acetyltransferase 2

ncRNA:

Noncoding RNA

NF1:

Neurofibromin 1

NKG2D:

Natural killer cell lectin-like receptor subfamily 2D

OPCML:

Opioid binding protein/cell adhesion molecule-like

p14arf:

An alternative reading frame product of the CDKN2A locus

p16:

Cyclin-dependent kinase inhibitor protein p16 (INK4a)

PBRM1:

Protein polybromo-1

pCCA:

Perihilar cholangiocarcinoma

PD-1/PD-L2:

Programmed cell death 1/programmed death ligand 2

PI3KCA:

Phosphoinositide 3-kinase p110

PIGR:

Polymeric immunoglobulin receptor

PTEN:

Phosphatase and tensin homolog

RAD51AP1:

RAD51 associating protein-1

RASSF1A:

Ras association domain family 1 isoform A

ROS1:

ROS proto-oncogene 1

shRNA:

Short hairpin RNA

SIN1:

Stress-activated map kinase-interacting protein 1

Axin-1:

Axis inhibition protein 1

SMAD4:

Small body mothers against decapentaplegic 4

SOCS3:

Suppressor of cytokine signaling 3

TGF-β:

Transforming growth factor-β

TP53:

Tumor protein p53

TYMS:

Thymidylate synthetase

UNG:

Uracil nucleotide glycosidase

VNN1:

Vanin1

XRCC1:

X-ray repair cross-complementing protein 1

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Acknowledgments

The authors thank Drs. Sopit Wongkham and Atit Silsirivanit (Khon Kaen University, Thailand) for continuous support and encouragement.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

    Sukanya Luang

  2. Gene Osaka Clinic Inc., Osaka, Japan

    Masahiko Minamiya

  3. Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Nobuo Sakaguchi

  4. Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya-ku, Tokyo, Japan

    Nobuo Sakaguchi

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  1. Sukanya Luang
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Correspondence to Nobuo Sakaguchi .

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  1. Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA

    James H. Tabibian

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Luang, S., Minamiya, M., Sakaguchi, N. (2021). Biochemical Indicators of Cholangiocarcinoma. In: Tabibian, J.H. (eds) Diagnosis and Management of Cholangiocarcinoma. Springer, Cham. https://doi.org/10.1007/978-3-030-70936-5_6

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