Dataset Information

High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma.

ABSTRACT:

Background

The incidence, prevalence, and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7 (PTK7) is upregulated in many common human cancers. However, its expression in ICC has not been studied. The present study aimed to explore the underlying mechanism of PTK7 in ICC.

Materials and methods

The role of PTK7 was studied in vitro by suppressing PTK7 expression in ICC cell lines. The in vivo effect of PTK7 was evaluated using a nude mouse model inoculated with a human ICC cell line. We also examined the role of PTK7 in human ICC samples.

Results

Cells with high PTK7 expression exhibited higher proliferation, DNA synthesis, invasion, and migration abilities than did cells with low PTK7 expression. The knockdown of PTK7 with small interfering RNA (siRNA) in high PTK7 expressing cells resulted in impairment of invasion, migration, and DNA synthesis through the regulation of several cell-cycle-related proteins. It also induced cell apoptosis and decreased phospho-RhoA expression. In a xenograft nude mouse model, PTK7 siRNA resulted in a reduction of the tumor size, compared with scrambled siRNA injection. PTK7 expression was higher in human ICC than in the normal bile duct. Patients with low expression of PTK7 had a longer disease-free survival and overall survival than those with high expression.

Conclusions

PTK7 expression plays an important role in the invasiveness of ICC cells and leads to a poor prognosis in ICC patients. Thus, PTK7 can be used as a prognostic indicator, and the inhibition of PTK7 expression could be a new therapeutic target for ICC.

SUBMITTER: Jin J

PROVIDER: S-EPMC3938661 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma.

Jin Jing J Ryu Han Suk HS Lee Kyoung Bun KB Jang Ja-June JJ

PloS one 20140228 2

<h4>Background</h4>The incidence, prevalence, and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7 (PTK7) is upregulated in many common human cancers. However, its expression in ICC has not been studied. The present study aimed to explore the underlying mechanism of PTK7 in ICC.<h4>Materials and methods</h4>The role of PTK7 was studied in vitro by suppressing PTK7 expression in ICC cell lines. The in vivo effect of PTK7 was evaluated using a ...[more]

PMID: 24587299

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Project description:BackgroundSeveral systemic inflammatory response (SIR) markers, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and albumin-to-globulin ratio (AGR), have emerged as prognostic markers in various cancers. The aim of this study was to explore the impact of SIR markers on the survival outcomes of unresectable intrahepatic cholangiocarcinoma (IHC) patients.MethodsPatients with histologically confirmed, unresectable IHC treated with gemcitabine plus cisplatin (GP) chemotherapy in a single tertiary hospital from 2012 to 2016 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were determined using unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis. Time-dependent receiver operating characteristic (ROC) analysis was performed to compare the performance of the SIR markers in predicting OS.ResultsA total of 137 patients received a median of six cycles (interquartile range [IQR], 3-11) of GP chemotherapy with a median observation time of 9.9 months (range, 1.8-54.7 months). The median PFS and OS of all patients were 7.8 months and 9.9 months, respectively. Among the SIR markers, high PLR (> 148) and high NLR (> 5) were associated with a short PFS (Hazard ratio [HR] 1.828, P = 0.006; HR 1.738, P = 0.030, respectively) and short OS (HR 2.332, P < 0.001; HR 2.273, P < 0.001, respectively). Low LMR (< 3.5) and low AGR (< 1.2) were associated with a short OS (HR 2.423, P < 0.001; HR 1.768, P = 0.002, respectively). In multivariable cox-regression analysis, high PLR (HR 1.766, P = 0.009) and distant lymph node (LN) metastasis (HR 2.085, P = 0.001) were associated with a short PFS. High PLR (HR 1.856, P = 0.002) was an independent predictor of a short OS, along with distant LN metastasis (HR 1.929; P < 0.001), low LMR (HR 1.691; P = 0.041), and low level of serum albumin (< 3.5 g/dL) (HR 1.632; P = 0.043). Time-dependent ROC analysis revealed that the area under the curve of PLR for predicting overall survival was greater than that of NLR, LMR, and AGR at most time points.ConclusionsHigh PLR was an independent prognostic factor of a short PFS and OS in patients with unresectable IHC receiving GP chemotherapy.

Dataset Information

High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma.

Background

Materials and methods

Results

Conclusions

Publications

High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma.

Similar Datasets

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