Clinicopathological characteristics of intrahepatic cholangiocarcinoma according to gross morphologic type: cholangiolocellular differentiation traits and inflammation- and proliferation-phenotypes

Abstract Background CyclinD1 is crucial for cell cycling and can regulate the expression of Dicer, a crucial regulator of microRNA maturation. However, little is known on how CyclinD1 regulates Dicer and miRNA expression, and the progression of intrahepatic cholangiocarcinoma (ICC). Methods The expression of CyclinD1 and Dicer in non-tumor cholangiocytes, ICC cells and tissues as well as their association with clinicopathological characteristics and survival were examined. The potential mechanisms by which CyclinD1 regulates Dicer and relative miRNA expression were determined by immunoprecipitation, ChIP sequence, BSP and luciferase reporter assays following induction of CyclinD1 over-expression or silencing and Dicer silencing. The impact of CyclinD1 and/or Dicer silencing on the growth of ICC was tested in vivo. Results Up-regulated CyclinD1 was associated with down-regulated Dicer expression in ICC tissues and poorer overall survival in patients with ICC. CyclinD1 interacted with the nuclear H3K9me3 and SUV39H1 and bound to the Dicer promoter to increase its CpG island methylation in ICC cells. Functionally, CyclinD1 silencing inhibited the malignancy of ICC cells, which were mitigated partially by Dicer silencing in ICC cells. Dicer silencing down-regulated miR-1914-5p and miR-541-5p expression, which targeted and promoted CyclinD1 and CDK6 expression in ICC cells. Conclusions Our findings uncover that CyclinD1 inhibits Dicer expression by chromatin modification to reduce miR-1914-5p/miR-541-5p expression, which positively-feedback enhances CyclinD1 and CDK6 expression and progression of ICC.

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Clinicopathological characteristics and prognostic factors for intrahepatic cholangiocarcinoma: a population-based study

Scientific Reports ◽

10.1038/s41598-021-83149-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tian-hua Yu ◽

Xin Chen ◽

Xuan-he Zhang ◽

Er-chi Zhang ◽

Cai-xia Sun

Keyword(s):

Intrahepatic Cholangiocarcinoma ◽

Tumor Size ◽

Population Based ◽

Clinicopathological Characteristics ◽

Elderly Age ◽

Related Factors ◽

Female Ratio ◽

Ajcc Stage ◽

Asian Pacific ◽

Stratified Analysis

AbstractWe aimed to explore the clinicopathological features and survival-related factors for intrahepatic cholangiocarcinoma (ICC). Eligible data were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015. Totally, 4595 ICC patients were collected with a male to female ratio of nearly 1:1. The higher proportion of ICC patients was elderly, tumor size ≥ 5 cm and advanced AJCC stage. Most patients (79.2%) have no surgery, while low proportion of patients receiving radiotherapy (15.1%). The median survival was 7.0 months (range 0–153 months). The 5-year CSS and OS rates were 8.96% and 7.90%. Multivariate analysis found that elderly age (aged ≥ 65 years old), male, diagnosis at 2008–2011, higher grade, tumor size ≥ 5 cm, and advanced AJCC stage were independent factors for poorer prognosis; while API/AI (American Indian/AK Native, Asian/Pacific Islander) race, married, chemotherapy, surgery and radiotherapy were independent favorable factors in both CSS and OS. Furthermore, stratified analysis found that chemotherapy and radiotherapy improved CSS and OS in patients without surgery. Age, sex, race, years of diagnosis, married status, grade, tumor size, AJCC stage, surgery, chemotherapy and radiotherapy were significantly related to prognosis of ICC. Chemotherapy and radiotherapy could significantly improve survival in patients without surgery.

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Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.349 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 349-349

Author(s):

Gaya Spolverato ◽

Yuhree Kim ◽

Sorin Alexandrescu ◽

Hugo Marques ◽

Luca Aldrighetti ◽

...

Keyword(s):

Median Survival ◽

Intrahepatic Cholangiocarcinoma ◽

Systemic Chemotherapy ◽

Disease Free Survival ◽

Best Supportive Care ◽

Clinicopathological Characteristics ◽

Nodal Metastasis ◽

Curative Intent ◽

Initial Surgery ◽

Repeat Hepatic Resection

349 Background: Many patients develop recurrence following resection of intrahepatic cholangiocarcinoma(ICC). Management and outcomes of patients with recurrent ICC following previous curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Methods: Between 1990-2013, 542 patients who underwent surgery for ICC were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence and recurrence-related management were recorded and analyzed. Results: At initial surgery, treatment was resection only(96.1%) or resection+RFA(3.9%). Overall 5-year survival was 25.9%; 376(69.4%) patients recurred with a median disease-free survival of 11.0 months. Vascular invasion(hazard ratio [HR]=1.43), nodal metastasis(HR=1.40) and poor differentiation(HR=1.30) were predictive of recurrence(all P<0.05). First recurrence site was intrahepatic only (62.0%), extrahepatic only (14.1%), or intra- and extrahepatic(23.9%). Overall 259(68.9%) patients received treatment for recurrent ICC, while 117(31.1%) received best supportive care(BSC). Among patients who received treatment for recurrent disease, therapy consisted of systemic chemotherapy only(49.4%), repeat liver-directed therapy (25.9%), or systemic chemotherapy+liver-directed therapy(24.7%). Repeat liver-directed therapy consisted of repeat hepatic resection±ablation(30.5%), ablation alone (21.4%), and intra-arterial therapy(IAT)(48.1%). Among patients who recurred, median survival from the time of the recurrence was 11.0 months(BSC-7.7 months, systemic chemotherapy only-10.0 months, liver-directed therapy-18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 7.6 months for patients who had IAT(P<0.001). Conclusions: Recurrence following resection of ICC is common, occurring in up to two-thirds of patients. When recurrence occurs, prognosis is poor. In well-selected patients with liver only recurrence, resection+chemotherapy may offer a modest survival benefit.

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