Dataset Information

Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer.

ABSTRACT:

Background

The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor cell growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine biological significance of LAT1 expression and investigate whether LAT1 could be a prognostic biomarker for biliary tract cancer.

Methods

A total of 139 consecutive patients with resected pathologic stage I-IV biliary tract adenocarcinoma were retrospectively reviewed. Tumor specimens were stained by immunohistochemistry for LAT1, Ki-67, microvessel density determined by CD34, and p53; and prognosis of patients was correlated. Biological significance of LAT1 expression was investigated by in vitro and in vivo experiments with LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using cholangiocarcinoma cell line.

Results

In total patients, high LAT1 expressions were recognized in 64.0%. The expression of LAT1 was closely correlated with lymphatic metastases, cell proliferation and angiogenesis, and was a significant indicator for predicting poor outcome after surgery. LAT1 expression was a significant independent predictor by multivariate analysis. Both in vitro and in vivo preliminary experiments indicated that BCH significantly suppressed growth of the tumor and yielded an additive therapeutic efficacy to gemcitabine and 5-FU.

Conclusions

High expression of LAT1 is a promising pathological marker to predict the outcome in patients with biliary tract adenocarcinoma. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.

SUBMITTER: Kaira K

PROVIDER: S-EPMC4016614 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer.

Kaira Kyoichi K Sunose Yutaka Y Ohshima Yasuhiro Y Ishioka Noriko S NS Arakawa Kazuhisa K Ogawa Tetsushi T Sunaga Noriaki N Shimizu Kimihiro K Tominaga Hideyuki H Oriuchi Noboru N Itoh Hideaki H Nagamori Shushi S Kanai Yoshikatsu Y Yamaguchi Aiko A Segawa Atsuki A Ide Munenori M Mori Masatomo M Oyama Tetsunari T Takeyoshi Izumi I

BMC cancer 20131016

<h4>Background</h4>The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor cell growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine biological significance of LAT1 expression and investigate whether LAT1 could be a prognostic biomarker for biliary tract cancer.<h4>Methods</h4>A total of 139 consecutive patients with resecte ...[more]

PMID: 24131658

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Project description:Background: Sarcopenia, systemic inflammation, and low muscularity significantly impact the survival of cancer patients. However, few studies have investigated how sarcopenia and systemic inflammation affect the prognosis of biliary tract cancer with distant metastasis. In this study, we investigated the association between sarcopenia with systemic inflammation and prognosis of metastatic biliary tract cancer. Materials and Methods: Data collected from 353 metastatic biliary tract cancer patients from 2007 to 2016 were analyzed. To evaluate the skeletal muscle mass, computed tomography images at the upper level of the third lumbar vertebra (L3) were used. Sarcopenia was defined using the Japan Society of Hepatology guideline; L3 muscle index <42 cm2/m2 for male and <38 cm2/m2 for female patients. Systemic inflammation was evaluated using the neutrophil lymphocyte ratio (NLR). Patients with NLR > 3 were categorized into the inflammatory category. The overall survival (OS) and progression free survival (PFS) were analyzed. Subgroup analysis was performed on those who received gemcitabine/cisplatin (GP) chemotherapy and depending on the presence of sarcopenia and inflammation. Results: Patients with sarcopenia showed lesser 1-year OS than those without (25.5 vs. 38.2%, p = 0.019). The patients with high NLR (NLR > 3) were associated with a shorter OS than were those with a low NLR (NLR ≤ 3) (21.0 vs. 52.8%, p < 0.001). Based on these results, we categorized the patients into three groups; sarcopenia accompanied by high NLR, no sarcopenia and low NLR, and either sarcopenia or high NLR. The OS of patients was well-stratified according to this grouping (1-year OS; 18.3 vs. 30.3 vs. 55.8%, p < 0.001). Concordant with OS results, the PFS was well-stratified based on the presence of either sarcopenia or high NLR (Sarcopenia; 9.5 vs. 19.4%, p < 0.001, NLR; 10.0 vs. 23.4%, p < 0.001). The PFS was significantly associated with high NLR and sarcopenia (1-year PFS; 7.8 vs. 13.0 vs. 27.9%, p < 0.001). Conclusion: Sarcopenia with inflammation was associated with inferior OS and PFS. In addition, sarcopenia accompanied by inflammation was associated with poor prognosis. Conservative treatments such as nutritional support, exercise, and pharmacologic intervention could help metastatic biliary tract cancer patients to overcome sarcopenia and the inflammatory status.

Project description:Background and objectiveNumerous previous studies have assessed the prognostic role of 18F-fluorodeoxyglucose positron-emission tomography (18F FDG PET) in patients with biliary tract cancer (BTC), but those results were inconsistent. The present study aims to determine the predictive value of 18F FDG PET in BTC patients via a meta-analysis.MethodsThe underlying studies related to 18F FDG PET and BTC patients` outcomes were searched and identified in the online databases. The interested parameters include total lesion glycolysis (TLG), metabolic tumor volume (MTV), primary tumor and metastatic lymph node (LN) maximum standardized uptake value (SUVmax), as well as change of SUVmax (ΔSUVmax) during treatment. Overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were considered as the primary endpoints. Hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were defined as the effective measure and calculated by a pooled analysis. Publication bias was assessed by funnel plot, Bagg's and Egger's tests.ResultsTotally, 23 studies involving 1478 patients were included in the present meta-analysis. After a pooled analysis, it revealed that a high SUVmax was significantly associated with a poor OS (HR:2.07, 95%CI: 1.74-2.46, P = 0.000) and DFS (HR: 2.28, 95%CI: 1.53-3.41, P = 0.000). In addition, an increased TLG level contributed to a shorter OS (HR:1.91, 95%CI: 1.26-2.90, P = 0.002) and DFS (HR: 4.34, 95%CI: 1.42-13.27, P = 0.01). Moreover, we confirmed that an elevated MTV was significantly associated with increased mortality (HR:2.04, 95%CI:1.26-3.31, P = 0.004) and disease relapse (HR: 3.88, 95%CI:1.25-12.09, P = 0.019) risks. Besides, the present study uncovered that increased ΔSUVmax could predict poor OS (HR:1.26, 95%CI:1.06-1.50, P = 0.008) instead of PFS (HR: 1.96, 95%CI: 0.82-4.72, P = 0.280). Lastly, we found that LN SUVmax did not link to OS (HR: 1.49, 95%CI: 0.83-2.68, P = 0.178). No obvious publication bias was detected in the present study.Conclusion18F FDG PET parameters, including SUVmax, TLG, MTV, and ΔSUVmax, could be applied as convenient and reliable factors for predicting BTC patients` outcomes.

Dataset Information

Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer.

Background

Methods

Results

Conclusions

Publications

Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer.

Similar Datasets

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