Open Access

Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma

  • Authors:
    • Jianhua Liu
    • Haosheng Jin
    • Hongxia Tian
    • Guoda Lian
    • Shaojie Chen
    • Jiayu Li
    • Xuchao Zhang
    • Dong Ma
  • View Affiliations

  • Published online on: November 4, 2015     https://doi.org/10.3892/ol.2015.3859
  • Pages: 213-223
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate anaplastic lymphoma kinase (ALK) status in hepatocellular carcinoma (HCC) and to evaluate whether abnormalities in expression were associated with patient prognosis. ALK status was investigated using immunohistochemistry (IHC), reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and fluorescence in situ hybridization (FISH) assays in 342 HCC patients. In addition, rapid amplification of complementary DNA ends‑coupled PCR sequencing was performed, in order to confirm the presence of ALK abnormalities in patients exhibiting ALK messenger RNA (mRNA) overexpression. The correlation between ALK expression and the clinicopathological features and prognosis of the HCC patients was statistically analyzed. The results of the present study revealed overexpression of ALK protein and mRNA; furthermore, ALK gene copy number gains were observed via IHC (44.7%; 153/342), RT‑qPCR (47.4%; 162/342) and FISH (32.7%; 112/342) analyses, although ALK rearrangement or mutation was not demonstrated in the results of any of these assays. ALK protein expression levels were significantly associated with hepatitis C virus (HCV) status (P<0.001) and the presence of micrometastases (P=0.011). Within the entire patient cohort, ALK expression was associated with poor progression‑free survival (PFS; P=0.041). Subsequent analysis in patient subgroups that demonstrated hepatitis B surface antigen positivity, HCV negativity, stage III‑IV disease, recurrence and micrometastasis positivity revealed that overall survival (OS) and PFS were significantly reduced in those patients exhibiting ALK expression compared with those patients who were negative for ALK expression. Multivariate analysis revealed that ALK expression was an independent risk factor for OS (P=0.042) and PFS (P=0.033), particularly for patients with stage III‑IV tumors. Thus, ALK may serve as a novel indicator for the metastatic behavior and prognosis of HCC.
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January-2016
Volume 11 Issue 1

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Spandidos Publications style
Liu J, Jin H, Tian H, Lian G, Chen S, Li J, Zhang X and Ma D: Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma. Oncol Lett 11: 213-223, 2016
APA
Liu, J., Jin, H., Tian, H., Lian, G., Chen, S., Li, J. ... Ma, D. (2016). Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma. Oncology Letters, 11, 213-223. https://doi.org/10.3892/ol.2015.3859
MLA
Liu, J., Jin, H., Tian, H., Lian, G., Chen, S., Li, J., Zhang, X., Ma, D."Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma". Oncology Letters 11.1 (2016): 213-223.
Chicago
Liu, J., Jin, H., Tian, H., Lian, G., Chen, S., Li, J., Zhang, X., Ma, D."Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma". Oncology Letters 11, no. 1 (2016): 213-223. https://doi.org/10.3892/ol.2015.3859