Survival Of Cholangiocarcinoma Patients Research Articles

Comprehensive analysis of the clinical and biological significances for chemokine CXCL3 in cholangiocarcinoma.

Cholangiocarcinoma (CHOL) is a race malignant cancer arising from bile duct epithelial cells in clinical practice. C-X-C motif chemokine ligand 3 (CXCL3) is a member of chemokines family, which participates in the pathogenesis of various tumors. However, the association between CXCL3 and CHOL is unclear. This present study was to assess the role of CXCL3 expression in the progress of CHOL. TIMER, GEPIA, UALCAN, GSCA, LinkedOmics, Metascape and STRING databases were performed to evaluate the clinical and biological significances for CXCL3 with CHOL patients including expression, clinicopathological factors, immune cell infiltration, GO enrichment and KEGG pathway analyses, as well as PPI network analysis. The immunohistochemistry analysis of tissue microarray was conducted to detect the protein expression level, subcellular localization, clinicopathological factors and prognosis of CXCL3 in CHOL. The mRNA and protein expression levels of CXCL3 were markedly increased in CHOL tissues. The overexpression of CXCL3 was strongly associated with maximum tumor diameter of patients with CHOL. Additionally, there were negative correlations between the expression of CXCL3 and monocyte as well as Th17. Low infiltration of neutrophil indicated significantly shorter cumulative survival in CHOL patients. And CXCL3 was significantly associated with arm-level deletion of CD8+ T cell. Furthermore, functional network analysis suggested that CXCL3 and its associated genes were mainly enriched for chemotaxis, secretory granule membrane, cytokine activity and IL-17 signaling pathway. CXCL3 might potentially participate in the carcinogenesis of CHOL, which provided a direction for future research on the mechanism of CXCL3 in CHOL.

The predictive value of lymphocyte to monocyte ratio for overall survival in cholangiocarcinoma patients with hepatic resection.

There is considerable heterogeneity in clinical behavior and survival outcomes in patients with cholangiocarcinoma (CCA), and the prognosis of CCA patients is poor. We proposed lymphocyte to monocyte ratio (LMR) as a novel prognostic element for CCA patients with hepatic resection in present study. By retrospectively analyzing the clinical data of 145 CCA patients with hepatic resection, we determined the optimal LMR cutoff value according to the receiver operating characteristic (ROC). We comparatively analyzed the clinical features of CAA patients between low LMR group and high LMR group, mainly including overall survival (OS) analysis by using the Kaplan-Meier method, univariate and multivariate Cox regression. We found there was a longer OS in CCA patients of the high LMR group than the low LMR group. The total median OS of cholangiocarcinoma patients were 13.6 months, and the OS of low LMR group was markedly lower than the high LMR group. The 1-year, 3-year, and 5-year OS of high LMR group were respectively 62.9%, 32.4%, and 16.4%, and were significantly higher the cholangiocarcinoma patients of low LMR group (40.2%, 16.4%, and 0%). Multivariate regression analyses showed that preoperative cholangitis, elevated CEA level and nerve invasion were risk factors for the OS of cholangiocarcinoma patients, while the high LMR level and postoperative treatment were protective factors for the OS of cholangiocarcinoma patients. Preoperative LMR was a vital prognostic factor to predict the prognosis of CCA patients with hepatic resection and provided additional prognostic value beyond standard clinicopathological parameters.

MRPL27 contributes to unfavorable overall survival and disease-free survival from cholangiocarcinoma patients.

Objective: This study aimed to investigate the roles of MRPL27 in survival from cholangiocarcinoma patients in The Cancer Genome Atlas (TCGA) database.Methods: In TCGA-CHOL profile, MRPL27 gene expression and clinical data were obtained. Cox regression models were used to evaluate the potential links between MRPL27 and cholangiocarcinoma survival. Enrichment analysis of MRPL27 was conducted in Metascape and Gene Set Enrichment Analysis (GSEA) databases.Results: 36 cholangiocarcinoma patients were included in this analysis. MRPL27 mRNA was significantly upregulated in tumor tissues in cholangiocarcinoma patients including intrahepatic, distal and hilar/perihilar cholangiocarcinoma cases (all p < 0.01). Cholangiocarcinoma patients with high MRPL27 had worse overall survival (OS) and disease-free survival (DFS) compared to those with low MRPL27 (all p < 0.05). Univariate and multivariate Cox models indicated that MRPL27 should be a risk factor for the OS and DFS in cholangiocarcinoma patients (both p < 0.01). Bioinformatic analysis revealed that MRPL27 mainly involved in the processes of mitochondrial translation elongation, respiratory electron transport, ATP synthesis, and inner mitochondrial membrane organization. No mutations of MRPL27 were screened in cholangiocarcinoma patients.Conclusion: Upregulated in tumors, MRPL27 contributes to unfavorable survival in cholangiocarcinoma patients.

Therapeutic Rationale to Target Highly Expressed Aurora kinase A Conferring Poor Prognosis in Cholangiocarcinoma.

Background: Cholangiocarcinoma is a highly lethal neoplasm for which the currently available chemotherapeutic agents are suboptimal. Numerous studies show that alterations in expression of genes related to mitotic spindle and mitotic checkpoint are involved in chromosomal instability and tumor progression in various malignancies. This study aimed to evaluate these genes in cholangiocarcinoma patients.Material and methods: Different public datasets were analyzed to examine the expression of 76 selected mitotic spindle checkpoint genes including Aurora Kinase A (AURKA) in cholangiocarcinoma. Afterwards, cell number counting, CCK-8 assay, and Caspase 3/7 assay were used to explore the antitumor effect of AURKA inhibitor Alisertib in vitro. In addition, xenograft model was used to evaluate the antitumor effect of Alisertib in vivo. Furthermore, siRNA mediated silencing of AURKA was used to verify the function of AURKA in cholangiocarcinoma.Results: Components of the mitotic spindle checkpoint, including AURKA, were broadly dysregulated in human cholangiocarcinoma. High AURKA mRNA expression was associated with poor survival in cholangiocarcinoma patients within different datasets. AURKA specific inhibitor Alisertib, inhibited cell growth, induced cell cycle arrest in G2/M phase, and promoted apoptosis in cholangiocarcinoma cell lines. Additionally, Alisertib also inhibited tumor growth in a cholangiocarcinoma xenograft mouse model. Furthermore, AURKA knockdown by siRNA recapitulated the antitumor effect of Alisertib. AURKA expression was also highly correlated with its interaction proteins Polo-like kinase 1(PLK1) and Targeting protein for xenopus kinesin-like protein2 (TPX2) in different cholangiocarcinoma datasets.Conclusions: Highly expressed AURKA confers poor outcomes in cholangiocarcinoma and may represent a rational therapeutic target.

188P - Survival and prognostic factors in cholangiocarcinoma: A single-center experience

BackgroundSurvival and prognosis data in cholangiocarcinoma patients in routine clinical practice has been limited. This study aimed to determine the survival of cholangiocarcinoma patients and to investigate prognostic factors for survival in cholangiocarcinoma patients. MethodsThis cohort study retrospectively reviewed 158 records of cholangiocarcinoma patients treated in Oncology Unit, Department of Medicine, Rajavithi hospital from 1 January 2004 to 31 December 2017. Clinical characteristics, treatments, and outcomes were collected and analyzed. ResultsThere were 158 patients whose median age was 58 years old while 69.6% of those had a good performance status (ECOG PS) of 0-1. The median survival time for all was 9.5 months (95% CI = 7.3-11.6) and the 1-year survival rate was 37.3%. After curative surgery (n = 49), 35 patients (71.4%) had tumor recurrence with the median disease-free survival of 8.81 months (95% CI = 6.93-10.68). Patients who received first-line palliative chemotherapy (n = 68) had the median progression-free survival of 4.3 months (95% CI = 3.51-5.10). The overall response rate to first-line chemotherapy was 7.3%. Variables analyzed by univariate analysis including ECOG PS of 3-4 (p < 0.001), neutrophil/lymphocyte ratio >/= 4 (p 0.004), intrahepatic cholangiocarcinoma (compared with hilar cholangiocarcinoma, p 0.005), distant metastasis in all sites (p < 0.001) and TNM stage IV disease (p < 0.001) were significant factors for shorter survival time. While surgical treatment, adjuvant chemotherapy and radiation, and palliative chemotherapy were significantly associated with better survival (p < 0.001). Multivariate analysis identified ECOG PS of 3-4 (p 0.001), intrahepatic type (p 0.001) and TNM stage IV disease (p 0.033) as independent poor prognostic factors for survival. Furthermore, receiving surgery and palliative chemotherapy administration (p < 0.001) were independent significant predictors associated with better survival compared to best supportive care alone. ConclusionsPoor ECOG performance status of 3, intrahepatic cholangiocarcinoma type and TNM stage IV disease were adverse prognostic factors whereas surgical treatment and palliative chemotherapy had a crucial role in treatment for cholangiocarcinoma patients. Legal entity responsible for the studyMedical Oncology unit, Internal Medicine Department, Rajavithi Hospital. FundingRajavithi Hospital. DisclosureAll authors have declared no conflicts of interest.

Impact of obesity upon the survival of cholangiocarcinoma patients.

288 Background: Obesity is a risk factor for developing cholangiocarcinoma (CCA). However, the effect of obesity on survival of CCA is unclear. The primary aim of this study was to analyze the impact of obesity upon overall survival of CCA patients. Secondary aims were to analyze impact of obesity upon other disease characteristics such as tumor site, stage, age, sex, BMI and Ca 19-9. Methods: A total of 411 unique pts diagnosed with CCA at Mayo Clinic Florida between 2000 and 2018 were retrieved from our collective SDMS database. Variables evaluated included:demographics, Body Mass Index (BMI), AJCC stage, tumor location and Ca 19-9.A total of 185 pts had all data available pertaining to these variables. We further restricted the analysis to pts with intrahepatic CCA classified BMI as per CDC criteria normal (18.5-25kg/m2), overweight (25-29.9kg/m2) and obese (≥30 kg/m2), thus leaving a total of 152 pts. Continuous and categorical variables were compared across BMI groups using Chi-squared or Fisher’s exact test. Overall survival rates after diagnosis at 1, 2 and 3 years were estimated using Kaplan-Meier method. Results: Among 152 pts included in the study, 28% were normal weight, 40% were overweight and 32% were obese. The overall survival rate at 1, 2 and 3 years for normal weight pts with all stages combined was 54.1%, 35%, and 30.7%, respectively. The overall survival rate at 1, 2 and 3 years for overweight pts with all stages combined was 59.7 %, 32.6%, and 25.4%, respectively. The overall survival rate at 1, 2 and 3 years for obese pts with all stages combined was 63.9%, 37.6%, and 26.7%, respectively(p = 0.8766). Multivariate analysis demonstrated is no significant difference in overall survival for obese pts compared to normal or overweight pts.(Table to be shown) However it showed, gender and Ca19-9 were statistically significant predictors of overall survival, with males and pts with Ca19-9≥100 doing worse (HR1.65 (CI = 1.05, 2.61, p = 0.031) and HR 2.31 (CI = 1.49, 3.59, p = &lt; 0.01), respectively). Conclusions: BMI did not make a significant impact on the overall survival, though there may be a trend toward worse OS for ptswith higher BMI. A larger, stage focused evaluation is warranted for further exploration of this trend.

Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery.

AIMTo clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in cholangiocarcinoma (CCA) subjects receiving surgery.METHODSIn this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics (including AAPR) were analyzed to determine predictors of post-operative overall survival and recurrence-free survival (RFS). In addition, univariate and multivariate Cox proportional hazards models were conducted, followed by application of time-dependent receiver operating curves to identify the optimal cut-off.RESULTSUnivariate and multivariate analyses revealed both decreased overall survival [hazard ratio (HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival (HR: 2.31, 95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥ 0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253 (83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low (< 0.41) AAPR group, which were significantly lower than those in the high (≥ 0.41) AAPR group (81.7%, 53.9%, and 33.4%, respectively) (P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.CONCLUSIONOur outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.

A novel three‑miRNA signature predicts survival in cholangiocarcinoma based on RNA‑Seq data

Accumulating evidence illustrates that many microRNAs (miRNAs) are abnormally expressed in cholangiocarcinoma and play important roles in tumorigenesis, tumor progression and metastasis. These miRNAs may serve as prognostic biomarkers and potential therapeutic targets. The aim of the present study was to identify the differentially expressed miRNAs in cholangiocarcinoma tissues vs. normal tissues by analyzing high‑throughput data derived from The Cancer Genome Atlas (TCGA) database. Furthermore, we evaluated the prognostic performance of the differentially expressed miRNAs and developed a novel three‑miRNA signature which predicted survival in cholangiocarcinoma patients. According to the cut‑off criteria of P<0.01 and |log2FC|>1.0, a total of 100miRNAs (54upregulated and 46downregulated) were found to be differentially expressed and some of them were significantly associated with clinical features. Of the above 100miRNAs, we obtained three miRNAs (miR‑10b, miR‑22 and miR‑551b) which were markedly related to patient overall survival (OS). Subsequently, a novel three‑miRNA signature was established and validated to be effective to predict survival. The results demonstrated that the survival rate, as well as the survival time of patients were obviously enhanced in relation to a lower miRNA signature index. Univariate and multivariate Cox regression analyses revealed that the three‑miRNA signature was an independent prognostic factor in cholangiocarcinoma. The reliability of the three‑miRNA signature was validated by an independent cohort from Gene Expression Omnibus (GEO). Furthermore, the functional enrichment analysis emphasized that the target genes of the aforementioned miRNAs may be involved in a variety of pathways and processes associated with cancer. Finally, these three miRNAs were detected for verification of expression using RT‑qPCR, and miR‑551b was selected for the verification of biological functions in cholangiocarcinoma cells. The results revealed that overexpression of miR‑551b decreased cancer cell proliferation and promoted apoptosis. Collectively, the results of the present study indicated that a specific three‑miRNA signature could be considered as an alternative prognostic marker in cholangiocarcinoma.

Value of modified Glasgow prognostic score in postoperative prognosis and survival of cholangiocarcinoma patients

Value of modified Glasgow prognostic score in postoperative prognosis and survival of cholangiocarcinoma patients

CXCL7 promotes proliferation and invasion of cholangiocarcinoma cells

CXCL7 is an important chemoattractant cytokine, which signals through binding to its receptor CXCR2. Recent studies have demonstrated that the CXCL7/CXCR2 signaling plays a promoting role in several common malignancies, including lung, renal, colon, and breast cancer. However, the regulatory role of CXCL7, in cholangiocarcinoma, as well as the underlying mechanism, has not been previously reported. Herein, we found more positive expression of CXCL7 in cholangiocarcinoma tissues compared to adjacent non-tumor tissues. High CXCL7 expression was significantly correlated with poor differentiation, lymph node metastasis, vascular invasion and advanced clinical stage, but was not associated with age, gender, or tumor size. Besides, the expression of CXCL7 was significantly associated with the Ki67 expression, but not associated with CA199, AFP, or P53 expression in cholangiocarcinoma. Moreover, the overall survival of cholangiocarcinoma patients with high CXCL7 expression was significantly shorter than those with low CXCL7 expression. Invitro study indicated that CXCL7 and CXCR2 were also positively expressed in several common cholangiocarcinoma cell lines, including HuCCT1, HuH28, QBC939, EGI-1, OZ and WITT. SiRNA-induced inhibition of CXCL7 significantly reduced the proliferation and invasion of QBC939 cells. On the contrary, overexpression of CXCL7 markedly promoted these malignant phenotypes of QBC939 cells. Of note, the conditioned medium of CXCL7-overexpresing human hepatic stellate cells could also promote the proliferation and invasion of QBC939 cells, suggesting that CXCL7 may also play an oncogenic role in cholangiocarcinoma in a paracrine-dependent manner, not only in an autocrine-dependent manner. Molecular assay data suggested that the AKT signaling pathway was involved in the CXCL7-mediated malignant phenotypes of QBC939 cells. In summary, our study suggests that CXCL7 plays a promoting role in regulating the growth and metastasis of cholangiocarcinoma.

Prognostic Significance of Neutrophil to Lymphocyte Ratio in Oncologic Outcomes of Cholangiocarcinoma: A Meta-analysis.

Increasing evidence indicates that the neutrophil to lymphocyte ratio (NLR) is a useful biomarker of long-term outcomes in patients with cholangiocarcinoma. However, the prognostic role of NLR in patients with cholangiocarcinoma remains unclear. Thus, the current meta-analysis was undertaken to clarify the correlation between NLR and overall survival (OS) in cholangiocarcinoma, and a comprehensive literature research was conducted to understand the association of NLR and prognosis of cholangiocarcinoma. The hazard ratio (HR) with 95% confidence interval (CI) was used to assess OS. The synthesized HR of 1.449 (95% CI: 1.296–1.619, P < 0.001) indicated that a high NLR had an unfavourable effect on OS. Overall, this meta-analysis suggested that elevated preoperative NLR is associated with poorer rates of survival in cholangiocarcinoma patients.

Health-Related Quality of Life and Survival of Cholangiocarcinoma Patients in Northeastern Region of Thailand.

In northeast Thailand, cholangiocarcinoma (CCA) is a major cause of mortality. Patients with CCA have a poor prognosis and short-term survival. The purpose of this study was to investigate the association between health-related quality of life (HRQOL) and survival time, and to explore whether change in HRQOL score is related to survival among CCA patients. The study was performed between February 2011 and January 2012, and included 171 patients with newly diagnosed CCA from 5 tertiary hospitals in four provinces of northeast Thailand. The HRQOL was measured at baseline, 1 month, and 2 months after diagnosis by the FACT-Hep questionnaire (Thai version 4). The outcome was survival time from diagnosis. Cox’s proportional hazard model was used to evaluate the association between HRQOL and survival time. A higher overall score on HRQOL was associated with a significantly better survival (HR per 5 units increase in HRQOL was 0.92, 95% CI: 0.88–0.96). Two of the separate domains contributing to the overall HRQOL—functional well-being and hepatobiliary cancer subscale—were found to have independent effects on survival, even after adjustment for potential confounding variables, and the other domains of HRQOL. CCA patient whose HRQOL scores had improved (≥9 units) at the 1st month of follow up had a reduced probability of dying from the disease (HR: 0.56, 0.32–0.95) after adjustment for the same confounding factors. A positive association between HRQOL at diagnosis and survival time was found. An improvement in HRQOL score in the first months after diagnosis further increases survival.

Clinical aspects and perspectives of erlotinib in the treatment of patients with biliary tract cancer

ABSTRACTIntroduction: Patients with non-resectable biliary tract cancer have a poor prognosis even if treated with systemic chemotherapy. One hope for improving treatment is through molecular biology and the characterization of specific cancer driving alterations followed by the design of targeted drugs. The epidermal growth factor receptor system is upregulated in many cancers and can be targeted by the protein kinase inhibitor erlotinib. Erlotinib has demonstrated a clinically applicable effect in pancreatic and lung cancerAreas covered: In this review, the author presents the published clinical data about erlotinib in biliary tract cancer. The data is interpreted with respect to its clinical value and in regards to its future development.Expert opinion: Erlotinib has low activity as a monotherapy, but has shown synergistic effects when combined with bevacizumab. The only phase III trial with erlotinib was negative, but suggested improved progression free survival in cholangiocarcinoma patients when added to gemcitabine and oxaliplatin. There is no clinical, radiological or molecular marker to guide therapy, but genomic profiling and basket or umbrella trials may be useful in identifying the subset of patients benefitting from erlotinib. Until this subgroup has been defined, erlotinib has no value to biliary tract cancer patients in the daily clinic.

Survival of Cholangiocarcinoma Patients in Northeastern Thailand after Supportive Treatment

Cholangiocarcinoma (CCA) is a very common cancer in Northeastern Thailand. Most CCA patients see a physician at a late stage when curative surgery is not possible. After diagnosis, they generally are treated by partial surgery/percutaneous drainage, chemotherapy and supportive treatment. This study aimed to assess the survival rates of CCA patients after supportive treatment. A retrospective cohort design was applied in this study. Data for 746 CCA patients were extracted from the hospital-based cancer registry of Srinagarind Hospital, Khon Kaen University. The patients were diagnosed (at least by ultrasonography) between 1 January, 2009 and 31 December, 2009 and then followed up for current status until 30 June, 2011. The cumulative survival rate was calculated by the Kaplan-Meier method, and independent prognostic factors were investigated using Cox regression. The total follow-up time was 5,878 person-months, and the total number of deaths was 637. The mortality rate was therefore 10.8 per 100 person-year (95%CI : 10.1-11.7). The cumulative 3, 6, 9, 12 and 24 month survival rates were 59%, 39%, 31%, 24% and 14%, respectively. The median survival time after supportive treatment was 4 months. After adjusting for gender, age, stage, distant metastasis, histological grading and treatment, stage was a significant predictor of survival of CCA patients. Those in stage III and stage IV had a 6.78 fold higher mortality than the stage I and stage II cases (95% CI : 1.6-28.7). It is very important to encourage patients to see health personnel at an early stage.

Impact of preoperative endoscopic ultrasound-guided fine needle aspiration on postoperative recurrence and survival in cholangiocarcinoma patients

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently performed for suspected biliary tumors for diagnosis and staging but carries a theoretical risk of needle-track seeding. We aimed to evaluate the impact of preoperative EUS-FNA on long-term outcomes for patients with cholangiocarcinoma (CCA). In a retrospective single-center study of consecutive patients with CCA with preoperative EUS-FNA, main outcome measures were overall survival and progression-free survival. In 150 patients with confirmed CCA, 61 underwent preoperative FNA. Median overall survival was 18.5 months (95% confidence limits [CL] 15.4, 25.7): 111 patients died and 39 survived. Of the 150 patients, 119 underwent curative-intent surgical resection, with median progression-free survival of 17.8 months (95% CL 14.5, 22.8); 89/119 patients had tumor recurrence or died, and 30/119 remained alive and disease-free. On multivariable analysis, overall survival was associated with: undergoing curative-intent surgery (hazard ratio [HR] 5.79, P = 0.001), lack of lymph node involvement (HR 1.89, P = 0.011), younger age (HR 1.51 for every 10 years, P < 0.0015), and small tumor size (HR 1.11 for every 1 cm, P = 0.029). For patients undergoing curative-intent surgery, on multivariable analysis, improved progression-free survival was associated with: lack of lymph node involvement (HR 1.88, P = 0.010), smaller tumor size (HR 1.16 for every 1 cm smaller, P = 0.003), and younger age (HR 1.53 for every 10 years, P < 0.001). Number of needle passes showed no statistically significant impact on overall survival. Preoperative EUS-FNA in patients with CCA does not appear to adversely affect overall or progression-free survival.

Differential Expression of Fascin, E-cadherin and Vimentin: Proteins Associated With Survival of Cholangiocarcinoma Patients

IntroductionThis study investigated the differential expression of fascin, E-cadherin and vimentin in human carcinogenesis. MethodsThis study detected their expressions in 142 cholangiocarcinoma and 20 benign bile duct tissue specimens using immunohistochemistry. Clinicopathologic characteristics and survival data were also collected and analyzed for their association with expression of these 3 proteins. ResultsThe data showed that both fascin and vimentin proteins were significantly overexpressed in cholangiocarcinoma, whereas E-cadherin expression was reduced in cholangiocarcinoma compared with normal tissues. Fascin protein expression was associated with tumor dedifferentiation, venous invasion and lymph node or distant metastasis. Similarly, vimentin expression was associated with tumor dedifferentiation and venous invasion, as well as hepatitis virus infection. In contrast, loss of E-cadherin expression was associated with tumor dedifferentiation (P<0.05). Because the functions of these 3 proteins were closely related, the data showed that fascin and E-cadherin protein expression was reversely associated. However, fascin and vimentin protein expression was positively associated with cholangiocarcinoma. Cox multiple regression analysis showed that distant tumor metastasis, tumor differentiation and overexpression of fascin and vimentin proteins were all independent risk factors for prognosis (P<0.05). ConclusionThe data from the current study demonstrated that overexpression of fascin and vimentin proteins could be further evaluated as biomarkers for the prediction of cholangiocarcinoma patient survival.

Abstract 1408A: Estrogen can stimulate cholangiocarcinoma cells proliferation and invasion and associate with poor prognosis

Abstract Cholangiocarcinoma is defined as a cancer arising from bile duct epithelial cell. The prevalence of cholangiocarcinoma is low among worldwide, however it was raised each year. Moreover, this kind of cancer is endemic in Thailand which associated with liver fluke infection, Opisthorchis viverrini. In Thailand, the prevalence of cholangiocarcinoma was about 20-time higher than in western country and may be more than 400-time in endemic area (northeastern part). Cholangiocarcinoma has poor prognosis with low 5-year survival rate due to its high metastasis rate which caused inadequate surgery while chemotherapy and radiotherapy are resisted. It is a type of chronic liver disease with altered estrogen metabolizing enzyme that could leading to the accumulation of estrogen in plasma. Estrogen was known as a promoting factor in progression of some cancer, eg. breast cancer and endometrial cancer. Our finding indicated the increasing of serum estrogen level in male cholangiocarcinoma patients and correlated with serum alkaline phosphatase and bilirubin and inverse correlated with albumin. The high level of serum estrogen could be determined as poor prognostic factor for survival of cholangiocarcinoma patients with statistically significant. In vitro studies demonstrated the effect of estrogen on cell proliferation and invasion of cholangiocarcinoma cell lines. Real time proliferative assay indicated the growth stimulated effect of estrogen on 4 cholangiocaricinoma cell lines (KKU-100, KKU-M055, KKU-M156 and KKU-M213) in dose dependent manner up to 10 nM. Results from in vitro invasion assay showed the effect of estrogen on cholangiocarcinoma cell invasion with highest effect at concentration 1 nM and this effect could be inhibited by tamoxifen. Metastasis genes expression of KKU-M213 cholangiocarcinoma cell induced by estrogen was measured by RT2 ProlifilerTM PCR array system. Total 84 metastasis genes expression were compared with non-induced cell, 24 genes showed change in expression level more than twice which were 11 genes increased and 13 genes decreased. The pathway of estrogen induced metastasis genes in cholangiocarcinoma cells should be analyzed. The results should indicate the mechanism and control of cholangiocarcinoma invasion and metastasis, which may be introduced to the new therapeutic guideline. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1408A. doi:10.1158/1538-7445.AM2011-1408A

PBK/TOPK in the differential diagnosis of cholangiocarcinoma from hepatocellular carcinoma and its involvement in prognosis of human cholangiocarcinoma

The increased expression of PDZ binding kinase/lymphokine-activated killer T-cell-originated protein kinase (PBK/TOPK) is associated with some human malignant tumors. In this study, we analyzed PBK/TOPK expression in hepatic primary tumor and explored its role in cholangiocarcinoma biology. Seventy-four cholangiocarcinomas, 33 hepatocellular carcinomas, and 10 normal liver tissues were prepared from paraffin-embedded specimens. PBK/TOPK protein was assessed by immunohistochemical staining, and the survival time was analyzed with the Kaplan-Meier method. The protein, mRNA of PBK/TOPK, and cell cycle of cholangiocarcinoma cell line after PBK/TOPK suppression with small interfere RNA were studied by Western blot, semiquantitative reverse transcriptase-polymerase chain reaction, and flow cytometry, respectively. PBK/TOPK was usually expressed in normal bile duct epithelial cells and much more frequently expressed in cholangiocarcinoma (68/74) but never expressed in hepatocytes and hepatocellular carcinomas (0/33). PBK/TOPK down-regulation was related to the poor prognosis of patients with cholangiocarcinoma (P = .013). Epidermal growth factor can enhance PBK/TOPK expression in cholangiocarcinoma QBC 939 cells, but suppression of PBK/TOPK in the cells did not affect their proliferation. PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients.

Incidence and prognosis of cholangiocarcinoma in Danish patients with and without inflammatory bowel disease: a national cohort study, 1978–2003

Patients with inflammatory bowel disease (IBD) are at increased risk of cholangiocarcinoma (CC), but quantitative data are scant. Furthermore, little is known about the impact of IBD on CC occurrence and prognosis. Based on nationwide population-based registries we compared the incidence and survival of CC patients with and without IBD from 1978 to 2003. We used the National Registry of Patients and the Danish Cancer Registry to identify patients with IBD and CC. From the Civil Registration System we identified population controls. We calculated incidence rates, incidence rate ratios (compared with population controls), and absolute cumulative risks. We also computed median survival in CC patients with and without IBD. 2,725 CC patients were identified. The incidence of CC among the 41,280 IBD patients was 7.6 per 100,000 person years compared with 1.9 per 100,000 among the 412,796 population controls (four-fold increased risk). The 10 year cumulative risk of CC in IBD patients was 0.07%. Sub analyses showed that the increased risk of CC was more pronounced in male IBD patients and in patients with ulcerative colitis. We found a decreasing CC incidence in IBD patients over calendar time. CC patients with IBD were, on average, 15 years younger at cancer diagnosis than IBD-free CC patients, and median survival was 1 month in both groups. In conclusion, the absolute risk of CC in IBD patients was low and the CC incidence decreased over calendar time. The prognosis was equally grave, regardless of the presence of IBD.