Increased level of nucleolin confers to aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma after hepatectomy

Abstract

BackgroundNucleolin, as a multifunctional protein, has been demonstrated to play an oncogenic role in human hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression pattern of nucleolin in HCC and determine its correlation with tumor progression and prognosis.MethodsNucleolin expression at both mRNA and protein levels in HCC and adjacent nonneoplastic tissues were respectively detected by quantitative real time polymerase chain reaction (Q-PCR), immunohistochemistry and western blotting.ResultsNucleolin expression, at both mRNA and protein levels, was significantly higher in HCC tissues than in the adjacent nonneoplastic tissues (both P < 0.001). In addition, the elevated nucleolin expression was markedly correlated with advanced tumor stage (P = 0.001), high tumor grade (P = 0.02) and serum AFP level (P = 0.008). Moreover, HCC patients with high nucleolin expression had shorter 5-year disease-free survival and shorter 5-year overall survival than those with low expression (both P < 0.001). Furthermore, the Cox proportional hazards model showed that nucleolin expression was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 3.696, 95% confidence interval [CI] = 1.662-8.138, P = 0.01) and 5-year overall survival (HR = 3.872, CI = 1.681-8.392, P = 0.01) in HCC.ConclusionThese results showed that the markedly and consistently increasing expression of nucleolin may be associated with aggressive characteristics of HCC, and implied that nucleolin expression may serve as a promising biochemical marker for predicting the clinical outcome of patients with this malignancy.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_175.

Meeting the needs of breast cancer: A nucleolin’s perspective

“…Nucleolin expression has been reported as a putative prognostic factor in several types of cancer 251,253,254,256,259,468 . In addition to its high expression, some studies suggested that the pattern of cellular expression correlated with tumor aggressiveness and a worse prognosis 251,[253][254][255]470 .…”

“…In our study, staining of cell surface nucleolin was not observed, in line with data generated with tumors from other histologic origin (pediatric intracranial ependymoma, non-small cell lung cancer, cervical or pancreatic ductal carcinoma) 255,258,259,468 . A literature review on this subject revealed great variability on the immunohistochemical staining pattern of nucleolin, making it difficult to compare results 251,[253][254][255][256][257][258][259]468,470 . Possible reasons for this might be the lack of antibodies that distinguish between cell-surface, cytoplasmic or nuclear protein.…”

“…Altogether, nucleolin's biological functions that contribute to cell homeostasis are also responsible for its role in the development of malignant traits under pathological conditions. In this respect, overexpression of nucleolin, and increased localization at the cell membrane, was shown in different cancer cell lines [243][244][245][246][247][248] and endothelial cells 249,250 , as well as in tumors of diverse histological origin [251][252][253][254][255][256][257][258][259] . Nucleolin overexpression contributes to tumorigenesis and cancer progression by supporting cancer cells proliferation and survival, and by promoting invasion and angiogenesis.…”

“…Recent studies have also reported nucleolin overexpression in human-derived tumor tissues as an unfavorable predictor, related to a higher risk of recurrence and worse overall survival of patients, in a variety of neoplasias 253,256,257,259,467,468 . Moreover, the predictive power of nucleolin in a pattern-dependent manner was shown for some types of neoplasias 251,253,254,257,469 .…”

AS1411 Aptamer-Decorated Biodegradable Polyethylene Glycol–Poly(lactic-co-glycolic acid) Nanopolymersomes for the Targeted Delivery of Gemcitabine to Non–Small Cell Lung Cancer In Vitro

“…54 On the other hand, it was proved that the increasing expression of nucleolin associated with aggressive characteristics of cancer tissues, and implied that nucleolin expression may serve as a promising biochemical marker for predicting the clinical outcome of patients with malignancy. 55 AS1411 is the first ssDNA aptamer to reach phase I and II clinical trials. 56 AS1411 can bind to nucleolin specifically and is subsequently internalized into the tumor cells, including in colorectal, breast, prostate, and non-small cell lung cancers.…”