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. 2019 Dec;7(23):744.
doi: 10.21037/atm.2019.12.37.

Cholangiocarcinoma: anatomical location-dependent clinical, prognostic, and genetic disparities

Hualian Hang  1 , Seogsong Jeong  1 , Meng Sha  1 , Defu Kong  1 , Zhifeng Xi  1 , Ying Tong  1 , Qiang Xia  1
Affiliations

Cholangiocarcinoma: anatomical location-dependent clinical, prognostic, and genetic disparities

Hualian Hang et al. Ann Transl Med. 2019 Dec.

Abstract

Background: Anatomical location is considered in diagnostic and therapeutic approaches of cholangiocarcinoma (CCA). However, disparities and its extents in proportion of surgical candidates, prognostic factors, prognostic genetic networks, susceptibility for lymph node dissection, and disease stage at diagnosis remain to be confirmed.

Methods: A total of 11,710 patients with cholangiocarcinoma from Surveillance, Epidemiology, and End Results Cancer Registries (SEER) and 45 CCA patients with paired tumor and normal specimens from The Cancer Genome Atlas were studied. Kaplan-Meier estimation, Cox proportional hazards regression, Pearson's correlation, comparison between anatomical location (distal, intrahepatic, and perihilar)-dependent CCAs, differential expressive gene stratification, potential interactive gene identification, and confirmation on pathways of the prognostic networks were carried out.

Results: Survival outcomes were most favorable in the distal type, followed by perihilar and intrahepatic types, but postsurgical prognosis was slightly higher in intrahepatic type compared to perihilar type. Distant historic stage at diagnosis was noticed in intrahepatic type. Significant prognostic factors and their hazards ratios were dependent to the anatomical location. In addition, lymph node dissection provided significant survival benefits in perihilar type only. Furthermore, prognosis-predictive genes, as well as potential processes and pathways, were significantly among the anatomical location-dependent types that the genes barely overlapped.

Conclusions: There are disparities in almost all aspects among distal, intrahepatic, and perihilar CCAs. Anatomical location needs to be considered in treatment, prognostic estimation, identifying targets, and developing therapeutic approaches for CCA.

Keywords: Biliary malignancy; bile duct cancer; distal cholangiocarcinoma (dCCA); intrahepatic cholangiocarcinoma (iCCA); perihilar cholangiocarcinoma (hiCCA).

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Trends and status of anatomical location-dependent CCAs. (A) Incidence, proportion of surgical candidates, survival rates, and disease stage at diagnosis for each CCA; (B) Kaplan-Meier curves for estimation of cumulative events between dCCA, iCCA, and hiCCA, including overall (first row) and surgical (second row) outcomes, in terms of overall survival and tumor-specific mortality; (C) Pearson’s correlation coefficient ranking for identification of each CCA-correlated variables. CCA, cholangiocarcinoma; dCCA, distal cholangiocarcinoma; iCCA, intrahepatic cholangiocarcinoma; hiCCA, perihilar cholangiocarcinoma.
Figure 2
Figure 2
Univariable and multivariable analyses for the overall survival to identify anatomical location-dependent prognostic factors in patients with CCA. CCA, cholangiocarcinoma.
Figure 3
Figure 3
Comparison of overall survival among subgroups of anatomical location-dependent CCAs. CCA, cholangiocarcinoma.
Figure 4
Figure 4
Top 10 prognostic genes predictive of survival outcomes for iCCA and hiCCA. (A) Top prognostic genes for overall survival; (B) top prognostic genes for recurrence-free survival; (C) a Venn diagram and circus plots for description of overlapping genes and between-gene interactions. iCCA, intrahepatic cholangiocarcinoma; hiCCA, perihilar cholangiocarcinoma.
Figure 5
Figure 5
Identification of prognostic network and its associated processes and pathways. (A) Development of the prognostic networks for iCCA and hiCCA; (B) identification of the prognostic networks-associated processes and pathways for iCCA and hiCCA. iCCA, intrahepatic cholangiocarcinoma; hiCCA, perihilar cholangiocarcinoma.
Figure S1
Figure S1
Pearson’s correlation coefficient ranking of demographic and clinical variables along with dCCA, iCCA, and hiCCA in the patients with CCA from TCGA database. dCCA, distal cholangiocarcinoma; iCCA, intrahepatic cholangiocarcinoma; hiCCA, perihilar cholangiocarcinoma.
Figure S2
Figure S2
Univariable and multivariable analyses for the tumor-specific survival to identify anatomical location-dependent prognostic factors in patients with CCA. CCA, cholangiocarcinoma.
Figure S3
Figure S3
Comparison of tumor-specific survival among subgroups of anatomical location-dependent CCAs. CCA, cholangiocarcinoma.
Figure S4
Figure S4
Volcano plots and heatmaps for stratification of significant prognostic genes for iCCA. First row: overall survival. Second row: recurrence-free survival. As for heatmaps, yellow and red are upregulated and down regulated genes, respectively. The thick bar on the left of the heatmaps are event (Blue) and no event (Pink). iCCA, intrahepatic cholangiocarcinoma.
Figure S5
Figure S5
Volcano plots and heatmaps for stratification of significant prognostic genes for hiCCA. First row: overall survival. Second row: recurrence-free survival. As for heatmaps, yellow and red are upregulated and down regulated genes, respectively. The thick bar on the left of the heatmaps are event (Blue) and no event (Pink). hiCCA, perihilar cholangiocarcinoma.
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References

    1. Labib PL, Goodchild G, Pereira SP. Molecular Pathogenesis of Cholangiocarcinoma. BMC Cancer 2019;19:185. 10.1186/s12885-019-5391-0 - DOI - PMC - PubMed
    1. Banales JM, Cardinale V, Carpino G, et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma. Nat Rev Gastroenterol Hepatol 2016;13:261-80. 10.1038/nrgastro.2016.51 - DOI - PubMed
    1. Khan SA, Davidson BR, Goldin RD, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut 2012;61:1657-69. 10.1136/gutjnl-2011-301748 - DOI - PubMed
    1. Kirstein MM, Vogel A. Epidemiology and Risk Factors of Cholangiocarcinoma. Visc Med 2016;32:395-400. 10.1159/000453013 - DOI - PMC - PubMed
    1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet 2014;383:2168-79. 10.1016/S0140-6736(13)61903-0 - DOI - PMC - PubMed