Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea.
Liver Int. 2018 Jan;38(1):113-124. doi: 10.1111/liv.13492. Epub 2017 Jul 10.
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse aetiologies, morphologies and clinical outcomes. Recently, histopathological distinction of cholangiolocellular differentiation (CD) of iCCA has been suggested. However, its genome-wide molecular features and clinical significance remain unclear.
Based on CD status, we stratified iCCAs into iCCA with CD (n=20) and iCCA without CD (n=102), and performed an integrative analysis using transcriptomic and clinicopathological profiles.
iCCA with CD revealed less aggressive histopathological features compared to iCCA without CD, and iCCA with CD showed favourable clinical outcomes of overall survival and time to recurrence than iCCA without CD (P<.05 for all). Transcriptomic profiling revealed that iCCA with CD resembled an inflammation-related subtype, while iCCA without CD resembled a proliferation subtype. In addition, we identified a CD signature that can predict prognostic outcomes of iCCA (CD_UP, n=486 and CD_DOWN, n=308). iCCAs were subgrouped into G1 (positivity for CRP and CDH2, 7%), G3 (positivity for S100P and TFF1, 32%) and G2 (the others, 61%). Prognostic outcomes for overall survival (P=.001) and time to recurrence (P=.017) were the most favourable in G1-iCCAs, intermediate in G2-iCCAs and the worst in G3-iCCAs. Similar result was confirmed in the iCCA set from GSE26566 (n=68).
CD signature was identified to predict the prognosis of iCCA. The combined evaluation of histology of CD and protein expression status of CRP, CDH2, TFF1 and S100P might help subtyping and predicting clinical outcomes of iCCA.
肝内胆管癌（iCCA）是一种具有异质性的实体瘤，其病因、形态和临床结局各不相同。最近，有人提出了 iCCA 的胆细胆管细胞分化（CD）的组织病理学区分。然而，其全基因组分子特征及其临床意义仍不清楚。
根据 CD 状态，我们将 iCCA 分为具有 CD（n=20）和不具有 CD（n=102）的 iCCA，并使用转录组和临床病理特征进行综合分析。
与不具有 CD 的 iCCA 相比，具有 CD 的 iCCA 具有侵袭性较弱的组织病理学特征，且具有 CD 的 iCCA 的总生存时间和复发时间均优于不具有 CD 的 iCCA（均 P<.05）。转录组分析显示，具有 CD 的 iCCA 类似于炎症相关亚型，而不具有 CD 的 iCCA 类似于增殖亚型。此外，我们确定了一个可以预测 iCCA 预后结果的 CD 特征（CD_UP，n=486 和 CD_DOWN，n=308）。将 iCCA 分为 G1（CRP 和 CDH2 阳性，7%）、G3（S100P 和 TFF1 阳性，32%）和 G2（其余，61%）。在 G1-iCCA 中，总生存时间（P=.001）和复发时间（P=.017）的预后结果最好，G2-iCCA 次之，G3-iCCA 最差。在 GSE26566 中的 iCCA 数据集（n=68）中也证实了这一结果。
CD 特征被确定可预测 iCCA 的预后。CD 的组织病理学和 CRP、CDH2、TFF1 和 S100P 蛋白表达状态的综合评估可能有助于 iCCA 的亚型分类和预测临床结局。
