scholarly journals The Emerging Role of miRNAs and Their Clinical Implication in Biliary Tract Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Nina Nayara Ferreira Martins ◽  
Kelly Cristina da Silva Oliveira ◽  
Amanda Braga Bona ◽  
Marília de Arruda Cardoso Smith ◽  
Geraldo Ishak ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Biliary Tract Cancers ◽  
Curative Therapy ◽  
Tract Cancer ◽  
Biliary Tract Tumors ◽  
Patients Experience

Biliary tract cancers are aggressive malignancies that include gallbladder cancer and tumors of intra- and extrahepatic ducts and have a poor prognosis. Surgical resection remains the main curative therapy. Nevertheless, numerous patients experience recurrence even after radical surgery. This scenario drives the research to identify biliary tract cancer biomarkers despite the limited progress that has been made. Recently, a large number of studies have demonstrated that deregulated expression of microRNAs is closely associated with cancer development and progression. In this review, we highlight the role and importance of microRNAs in biliary tract cancers with an emphasis on utilizing circulating microRNAs as potential biomarkers. Additionally, we report several single-nucleotide polymorphisms inmicroRNAgenes that are associated with the susceptibility of biliary tract tumors.

Role of adjuvant and neoadjuvant therapy for resectable biliary tract cancer.

2021 ◽  
Author(s):  
Satoshi Nara ◽  
Minoru Esaki ◽  
Daisuke Ban ◽  
Takeshi Takamoto ◽  
Takahiro Mizui ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tract Cancer ◽  
Adjuvant And Neoadjuvant Therapy

Prognostic value of dickkopf-1 and ß-catenin expression according to the antitumor immunity of CD8-positive tumor-infiltrating lymphocytes in biliary tract cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16172-e16172
Author(s):  
Seoree Kim ◽  
Yoon Ho Ko ◽  
Hye Sung Won ◽  
Ji Hyun Yang ◽  
Der Sheng Sun ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cox Regression ◽  
Research Network ◽  
Antigen Retrieval ◽  
Tract Cancer ◽  
Tissue Sections ◽  
Dkk1 Expression

e16172 Background: Despite recent advancements in the understanding of the molecular biology of biliary tract cancer (BTC), target therapy and immunotherapy have demonstrated only limited efficacy, with cytotoxic systemic therapy still being the most effective treatment in BTC, except for surgery. Thus, this study aimed to analyze the role of DKK1 or β-catenin as a prognostic factor in BTC and determine the clinical association of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocyte (TIL). Methods: We used data in The Cancer Genome Atlas (TCGA) Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections, and whole tissue sections of representative tumor samples were used for antigen retrieval. Results: CD8+TIL expression was a significant predictor of favorable overall survival (OS) and recurrence-free survival (RFS) (median OS, 34.9months in TIL-high, 16.7months in TIL-low, P < 0.0001 respectively; median RFS, 27.1months in TIL-high, 10months in TIL-low, P < 0.0001 respectively). Positive ß-catenin expression and high DKK1 expression was also associated with a shorter OS (median OS, 23.95months in positive ß-catenin, 26.1months in negative ß-catenin, P = 0.1009 respectively; median OS, 19.4months in high DKK1, 31.65months in Low DKK1, P = 0.0093 respectively), but not RFS (p = 0.1466, at ß-catenin respectively; p = 0.2924, in DKK1 respectively). In the CD8+TIL-high BTC group, the tumor expression of β-catenin and DKK1 had a significant negative impact on either OS or RFS (p = 0.0146 and p = 0.0112, at ß-catenin respectively; p = 0.0950 and p = 0.3904, in DKK1 respectively). However, in the TIL-low BTC group, there were no differences in OS or RFS according to ß-catenin and DKK1 expression (p = 0.5108 and p = 0.8431, at ß-catenin respectively; p = 0.1127 and p = 0.1095, in DKK1 respectively). Cox regression multivariate analysis demonstrated that CD8+ TIL (hazard ratio [HR], 0.490; 95% confidence interval (CI), 0.303-0.791; p = 0.004) and β-catenin (HR, 1.652; 95% CI, 1.035-2.639; p = 0.036) retained significant association with OS after adjustment for all variables. Conclusions: Among patients with resected BTC, β-catenin and DKK1 protein levels are associated with poor clinical outcomes, whereas high CD8+ TIL levels are associated with good clinical outcomes. This confirms the differential clinical role of Wnt/β-catenin and DKK1 proteins according to TIL expression in BTC.

Frequency of BRCA mutation in biliary tract cancer and its correlation with tumor mutational burden (TMB) and microsatellite instability (MSI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4085-4085 ◽  
Author(s):  
Gilbert Spizzo ◽  
Alberto Puccini ◽  
Joanne Xiu ◽  
Richard M. Goldberg ◽  
Axel Grothey ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Brca Mutation ◽  
Treatment Strategies ◽  
Missense Mutations ◽  
Brca Mutations ◽  
Extrahepatic Cholangiocarcinoma ◽  
Similar Frequency ◽  
Biliary Tract Cancers ◽  
Tract Cancer

4085 Background: Biliary tract cancers constitute ~3% of cancers worldwide with incidence increasing, especially for intrahepatic cholangiocarcinoma (IHC). The prognosis of these tumors remains dismal and novel treatment strategies are needed to improve overall survival. BRCA mutations occur in biliary tract cancers but their frequency in distinct sites of biliary tract cancer is unknown. Moreover, no data are available correlating BRCA mutation with immunogenic markers such as TMB, MSI, or PD-L1 expression. Methods: Tumor samples from 1288 primary biliary tract cancers, comprising IHC (n = 746), extrahepatic cholangiocarcinoma (EHC) (n = 189), gallbladder (GBC) (n=353) were profiled at Caris Life Sciences, Phoenix, AZ. Testing included NextGen SEQ (MiSeq on 47 genes, NextSeq on 592 genes) and PD-L1 IHC (SP142). TMB was calculated based on somatic nonsynonymous missense mutations, and MSI was evaluated by NGS of known MSI loci. Results: BRCA mutations were detected in 3.6% (N = 46) of samples ( BRCA1 0.6%, BRCA2 3%), no differences were seen based on the site of the tumor. In GBC and IHC BRCA2 mutations (4.0% and 2.7%) were more frequent than BRCA1 (0.3% and 0.4, p < 0.05) while in EHC, similar frequency was observed ( BRCA1: 2.1%; BRCA2: 2.6%). There was no significant association with gender or age. In BRCA-mutant biliary tract cancer the most frequently mutated genes were TP53 (55.6%), ARID1A (52.2%) and KRAS (26.1%), KMT2D/C (20%, 13%) and CDKN2A(13%). Overall, BRCA mutations were associated with a higher rate of MSI-H (19.5% vs 1.7%, p = 0.001) and higher TMB in both MSI-H and MSS tumors (p<0.05). When investigated separately, BRCA association with elevated TMB was seen in IHC and EHC, but not in GBC. No correlation was seen with PD-L1 expression. TP53, KMT2D/C, RB1, PTEN, KDM6A mutations and FGFR1 amplifications were significantly higher in BRCA mutated tumors (p < 0.05). Conclusions: BRCA mutations are found in a significant subgroup of biliary tract tumors and are associated with an immunogenic tumor profile. These data provide rationale for trials testing PARP inhibitors in combination with immunotherapy and targeted therapies in patients with BRCA-mutant biliary tract cancers that are MSS.

scholarly journals Prognostic role of programmed death-ligand 1 expression in patients with biliary tract cancer: a meta-analysis

Aging ◽  
2019 ◽  
Vol 11 (24) ◽  
pp. 12568-12580
Author(s):  
Changjiang Lei ◽  
Xiulan Peng ◽  
Xiaojun Gong ◽  
Ying Fan ◽  
Shenglin Wu ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
Tract Cancer ◽  
Programmed Death

scholarly journals Helicobacter pylori and Biliary Tract Cancers: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Soumia Cherif ◽  
Kaoutar Bouriat ◽  
Hanane Rais ◽  
Said Elantri ◽  
Abdessamad Amine
Keyword(s):  
Helicobacter Pylori ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Meta Analysis ◽  
Epidemiological Data ◽  
Case Control Studies ◽  
Chi Square ◽  
Biliary Tract Cancers ◽  
Tract Cancer ◽  
Increased Risk

Background. Helicobacter pylori is detected in various extragastric diseases, including biliary tract cancers. Besides, gallbladder cancers, extracholangiocarcinomas, and intracholangiocarcinomas are highly lethal cancers with limited survival due to their late diagnosis. Epidemiological data on Helicobacter pylori infection and biliary tract cancer have been contradictory. Aim. The aim of this study is to explore and evaluate the association between the Helicobacter pylori infection and biliary tract cancer. Materials and Methods. Systematic literature research was carried out to identify all eligible articles. All relevant publications from 2000 to 2019 were retrieved using comprehensive combinations of keywords. We used a random effects model to calculate pooled prevalence estimates, and 95% confidence intervals (CIs) for odds ratio were also calculated. Quantitative assessment of heterogeneity was explored by the chi-square test and was measured using I2. Results. Thirteen case-control studies published between 2001 and 2018 were included. The overall meta-analysis favoured a significant association between Helicobacter pylori infection and biliary tract cancer (OR, 2.57; 95% CI, 1.35–4.91; I2 = 58%). Geographic distribution-based subgroup analysis showed a higher prevalence of H. pylori in Asian and North American countries. Evidence supporting the higher presence of Helicobacter pylori in a cancer group was found by PCR. In another subgroup, the ORs were 4.18 (2.03, 8.58) in cholangiocarcinoma, 1.36 (0.34, 5.44) in gallbladder cancer, and 5.93 (1.89, 18.63) in other biliary tract cancers. Conclusion. This meta-analysis suggests that infection of the biliary tract with Helicobacter pylori is related to an increased risk of biliary tract cancers.

F-box and WD repeat domain-containing 7 (FBXW7) mRNA and outcome in biliary tract cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14521-e14521
Author(s):  
Gerardo F. Arroyo ◽  
Diego Kaen ◽  
Alejandro Salvatierra ◽  
Sandra Viviana Rojo ◽  
Ruben Dario Kowalyszyn ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Expression Levels ◽  
Tract Cancer ◽  
Repeat Domain ◽  
Hotspot Mutations

e14521 Background: Thestandard treatment for biliary tract cancer is gemcitabine plus platinum, but median progression-free survival (PFS) is only 5-8 months (m) (Valle et al, NEJM 2010). Gene expression or somatic mutations may influence the clinical phenotype, which will affect decisions on individualized treatment. Methods: We retrospectively analyzed tissue blocks from 54 advanced or metastatic cholangiocarcinoma, gallbladder or ampulllary cancer patients (p) treated with single-agent gemcitabine or gemcitabine plus carboplatin or cisplatin. Using RT-PCR, we analyzed the mRNA expression levels of oncogenes, tumor suppressors and DNA repair genes (BRCA1, RRM1, AEG-1, RAP80, SPINK1 and FBXW7) and correlated results with PFS, overall survival (OS) and response. In addition, FBXW7 hotspot mutations were assessed. Results: p characteristics: 72% females; median age, 60 (40-87). Only FBXW7 expression correlated with PFS and OS. When FBXW7 levels were dichotomized at the median value, PFS was 4.2 m for p with low levels vs 12.6 m for p with high levels (p=0.02). When FBXW7 expression was divided by terciles, PFS was 4.9 m for p in the lowest tercile, 7.6 for p in the intermediate tercile, and 26.9 m for p in the highest tercile (p=0.08). OS was 6.2 m for p in the lowest tercile, 8 m for p in the intermediate tercile, and not reached for p in the highest tercile. No other significant correlation was observed between expression levels of the other genes examined and PFS or OS. Only AEG-1 expression correlated with response (p=0.05). No FBXW7 hotspot mutations were detected. Conclusions: Although we did not find the FBXW7 hotspot mutations previously described in biliary tract cancer, FBXW7 mRNA expression significantly influenced PFS and OS. A separate cohort of p is being analyzed to validate the prognostic role of FBXW7.

LDH serum levels as prognostic and predictive factor in advanced biliary tract cancer patients treated with first-line chemotherapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 313-313
Author(s):  
Luca Faloppi ◽  
Michela Del Prete ◽  
Mario Scartozzi ◽  
Daniele Santini ◽  
Maristella Bianconi ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Serum Levels ◽  
First Line ◽  
Tract Cancer ◽  
Group A ◽  
Group B ◽  
Line Chemotherapy

313 Background: Previous data suggested that LDH serum levels may be associated with tumour hypoxia and VEGFA and VEGFR-1 over-expression. LDH may then represent an indirect marker of activated tumour neo-angiogenesis and worse prognosis in many tumour types. In our analysis, we analyzed the role of LDH serum levels in predicting clinical outcome for biliary tract cancer patients treated with first-line cisplatin and gemcitabine chemotherapy, to individuate a potentially reliable and easy to use marker for patients stratification. Methods: 71 advanced biliary tract cancer patients treated with cisplatin and gemcitabine in first-line chemotherapy were available for our analysis. For all patients, LDH values were collected within one month before treatment beginning. We chose the laboratory cut-off (Upper Normal Rate, UNR) as LDH cut-off value (450 U/l) and then we divided the patients into two groups (A and B, below and above the UNR respectively). Survival distribution was estimated by the Kaplan-Meier method. Disease control rate (DCR) was assessed with chi-square test. A significant level of 0.05 was chosen to assess the statistical significance. Results: Patients in group A (46 patients) and B (25 patients) proved homogeneous for all clinical characteristics analyzed. Median progression free survival (PFS) was 3.97 months and 1.8 months respectively in group A (patients with LDH level below the UNR) and in group B (patients with LDH level above the UNR), p=0.0064 (HR=2.07, 95%CI: 1.07-3.99). Median overall survival (OS) was 9.24 months and 2.55 months in group A and B respectively, p<0.0001 (HR=2.93; 95%CI: 1.37-6.27). DCR was 65% in group A vs. 21% in group B (p=0.004). Conclusions: Our observations seem to suggest a prognostic role of LDH in biliary tract cancer patients. Our findings showing an improved PFS and DCR in patients with low LDH serum levels also suggest a possible predictive role in patients treated with a cisplatin and gemcitabine regimen as first-line chemotherapy. After further confirmation in larger trial, these results may be relevant for a better patients stratification and selection.

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